rs8099917

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_StrongBA1

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

Scores

2

Clinical Significance

drug response reviewed by expert panel B:1O:2

Conservation

PhyloP100: 1.79
Variant links:

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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: {drug_response=2, Benign=1}.
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
show subpopulations
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
show subpopulations
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:1Other:2
Revision: reviewed by expert panel
LINK: link

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8099917; hg19: chr19-39743165; API