rs10509677

Variant names:

• chr10-94816353-T-C
• rs10509677
• NM_000769.4:c.820-4143T>C

Variant summary

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

The NM_000769.4(CYP2C19):​c.820-4143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 151,892 control chromosomes in the GnomAD database, including 231 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.047 (231 hom., cov: 30)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• Publications: 4 publications found

Genes affected

CYP2C19 (HGNC:2621): (cytochrome P450 family 2 subfamily C member 19) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, omeprazole, diazepam and some barbiturates. Polymorphism within this gene is associated with variable ability to metabolize mephenytoin, known as the poor metabolizer and extensive metabolizer phenotypes. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

ENSG00000276490 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C19	NM_000769.4	c.820-4143T>C		intron_variant	Intron 5 of 8	ENST00000371321.9	NP_000760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C19	ENST00000371321.9	c.820-4143T>C		intron_variant	Intron 5 of 8	1	NM_000769.4	ENSP00000360372.3
ENSG00000276490	ENST00000464755.1	n.*578-4143T>C		intron_variant	Intron 10 of 13	2		ENSP00000483243.1
CYP2C19	ENST00000645461.1	n.1873-26484T>C		intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 7212 AN: 151774 Hom.: 232 Cov.: 30

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0460

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0475 AC: 7209 AN: 151892 Hom.: 231 Cov.: 30 AF XY: 0.0480 AC XY: 3563 AN XY: 74242

African (AFR) AF: 0.0125 AC: 520 AN: 41514

American (AMR) AF: 0.0459 AC: 700 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3470

East Asian (EAS) AF: 0.0373 AC: 193 AN: 5172

South Asian (SAS) AF: 0.114 AC: 548 AN: 4810

European-Finnish (FIN) AF: 0.0498 AC: 518 AN: 10408

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0632 AC: 4295 AN: 67942

Other (OTH) AF: 0.0521 AC: 110 AN: 2112

Alfa AF: 0.0542 Hom.: 32

Bravo AF: 0.0444

Asia WGS AF: 0.0740 AC: 259 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.40
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10509677; hg19: chr10-96576110;