rs8099917

Variant names:

• chr19-39252525-T-G
• rs8099917

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.156 in 152,216 control chromosomes in the GnomAD database, including 2,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).

• Frequency: Genomes: 𝑓 0.16 (2231 hom., cov: 32)
• Consequence: Unknown
• Clinical Significance: drug response reviewed by expert panel B:1 O:2
• Conservation: PhyloP100: 1.79
• Publications: 1008 publications found

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23785 AN: 152098 Hom.: 2231 Cov.: 32

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.156 AC: 23797 AN: 152216 Hom.: 2231 Cov.: 32 AF XY: 0.153 AC XY: 11372 AN XY: 74420

African (AFR) AF: 0.0683 AC: 2839 AN: 41544

American (AMR) AF: 0.258 AC: 3944 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3470

East Asian (EAS) AF: 0.0654 AC: 339 AN: 5184

South Asian (SAS) AF: 0.153 AC: 738 AN: 4820

European-Finnish (FIN) AF: 0.129 AC: 1371 AN: 10606

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13237 AN: 68000

Other (OTH) AF: 0.174 AC: 368 AN: 2112

Alfa AF: 0.186 Hom.: 13627

Bravo AF: 0.165

Asia WGS AF: 0.105 AC: 367 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Benign:1 Other:2

Revision: reviewed by expert panel

Submissions by phenotype

not provided Benign:1

Mar 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

interferons, peginterferon alfa-2a, peginterferon alfa-2b, and ribavirin response - Efficacy Other:1

Mar 29, 2021

PharmGKB

Significance: drug response

Review Status: reviewed by expert panel

Collection Method: curation

PharmGKB Level of Evidence 1B: Level 1B clinical annotations describe variant-drug combinations with a high level of evidence supporting the association but no variant-specific prescribing guidance in an annotated clinical guideline or FDA drug label. Level 1B clinical annotations must be supported by at least two independent publications. Drug-variant association: Efficacy

peginterferon alfa-2a, peginterferon alfa-2b, ribavirin, and telaprevir response - Efficacy Other:1

Mar 24, 2021

PharmGKB

Significance: drug response

Review Status: reviewed by expert panel

Collection Method: curation

PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Efficacy

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.90
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs8099917; hg19: chr19-39743165;