rs8099917

Positions:

• chr19-39252525-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_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

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 19-39252525-T-G is Benign according to our data. Variant chr19-39252525-T-G is described in ClinVar as [drug_response]. Clinvar id is 226027.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_benign, oryginal submissions are: {Benign=1, drug_response=2}.
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	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

Gnomad4 AFR AF: 0.0683

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.0654

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.174

Alfa AF: 0.191 Hom.: 6932

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 14, 2018

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

drug response, reviewed by expert panel

curation

PharmGKB

Mar 29, 2021

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

drug response, reviewed by expert panel

curation

PharmGKB

Mar 24, 2021

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8099917; hg19: chr19-39743165;