An important epidemiological tool for just bonding to pandemics and monitoring is the sequencing of severe acute respiratory syndrome coronavirus 2 viral genome. The generation of coronavirus 2 genomic sequences from positive samples collected, along with epidemiological metadata was done. It was set up in the mission district of San Francisco, California from 22N21 December 2020 and 10 to 29 January 2021. A total of 12 124 tests were conducted yielding 1099 positives. 928 high-quality genomes were generated. Viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the “California” or “West Coast” variants (B.1.427 and B.1.429) were at higher risk of infection comparable to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, risk ratio [RR] = 1.28; 95% confidence interval [CI]: 1.00–1.64). Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%). Studies recorded a growing prevalence and modestly elevated attack for West Coast severe acute respiratory syndrome coronavirus to variants. Therefore the increasing rate in prevalence, relative houses attack rates are consistent with a modest transmissibility increase of the West Coast variants.