chr10-94761900-C-T

Variant names:

• chr10-94761900-C-T
• rs12248560
• ENST00000464755.1:n.932-13158C>T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Strong BA1

The ENST00000464755.1(ENSG00000276490):​n.932-13158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,940 control chromosomes in the GnomAD database, including 3,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★★).

• Frequency: Genomes: 𝑓 0.20 (3261 hom., cov: 32)
• Consequence: ENSG00000276490 ENST00000464755.1 intron
• Clinical Significance: drug response practice guideline B:1 O:3
• Conservation: PhyloP100: -0.799

Genes affected

ENSG00000276490 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 10-94761900-C-T is Benign according to our data. Variant chr10-94761900-C-T is described in ClinVar as [drug_response]. Clinvar id is 39357.Status of the report is practice_guideline, 4 stars. We mark this variant Likely_benign, oryginal submissions are: {other=1, drug_response=1, Benign=1}. Variant chr10-94761900-C-T is described in Lovd as [Benign]. Variant chr10-94761900-C-T is described in Lovd as [Benign]. Variant chr10-94761900-C-T is described in Lovd as [Pathogenic].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 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
ENSG00000276490	ENST00000464755.1	n.932-13158C>T		intron_variant	Intron 6 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30383 AN: 151824 Hom.: 3260 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.00945

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.200 AC: 30385 AN: 151940 Hom.: 3261 Cov.: 32 AF XY: 0.197 AC XY: 14601 AN XY: 74238

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.00947

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.198

Alfa AF: 0.222 Hom.: 483

Bravo AF: 0.196

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Significance: drug response

Submissions summary: Benign:1 Other:3

Revision: practice guideline

Submissions by phenotype

not provided Benign:1 Other:1

Jul 09, 2015

Eurofins Ntd Llc (ga)

Significance: other

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles).

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. -

CYP2C19: increased function Other:1

-

Clinical Pharmacogenetics Implementation Consortium

Significance: drug response

Review Status: practice guideline

Collection Method: curation

- Allele function

Clopidogrel response Other:1

-

Faculty of Pharmacy, Damascus University

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

rs12248560 is a SNP in the CYP2C19 gene and is linked to increased clopidogrel metabolic activation. rs12248560 is associated with increased enzyme activity of CYP2C19 and higher concentration of clopidogrel active metabolite. over responsive

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.27
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12248560; hg19: chr10-96521657;