rs12777823

Positions:

• chr10-94645745-G-A
• chr10-94645745-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.19 in 152,074 control chromosomes in the GnomAD database, including 3,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).

• Frequency: Genomes: 𝑓 0.19 (3069 hom., cov: 33)
• Consequence: Unknown
• Clinical Significance: drug response reviewed by expert panel O:1
• Conservation: PhyloP100: 0.0780

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28938 AN: 151956 Hom.: 3063 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.190 AC: 28965 AN: 152074 Hom.: 3069 Cov.: 33 AF XY: 0.194 AC XY: 14442 AN XY: 74320

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.169

Alfa AF: 0.163 Hom.: 2060

Bravo AF: 0.185

Asia WGS AF: 0.311 AC: 1079 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: reviewed by expert panel

Submissions by phenotype

warfarin response - Dosage Other:1

drug response, reviewed by expert panel

curation

PharmGKB

Apr 12, 2021

PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. Drug-variant association: Dosage

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	9.8
DANN	Benign	0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12777823; hg19: chr10-96405502;