chr10-94774827-G-A

Variant names:

• chr10-94774827-G-A
• rs7916649
• NM_000769.4:c.169-231G>A

Variant summary

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

The NM_000769.4(CYP2C19):​c.169-231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 537,854 control chromosomes in the GnomAD database, including 59,258 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 0.48 (18849 hom., cov: 32)
  • Exomes 𝑓: 0.45 (40409 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 18 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:):

MTND4P19 (HGNC:42206): (MT-ND4 pseudogene 19)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000769.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	NM_000769.4	MANE Select	c.169-231G>A		intron	N/A	NP_000760.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	ENST00000371321.9	TSL:1 MANE Select	c.169-231G>A		intron	N/A	ENSP00000360372.3
	CYP2C19	ENST00000480405.2	TSL:1	c.169-231G>A		intron	N/A	ENSP00000483847.1
	ENSG00000276490	ENST00000464755.1	TSL:2	n.932-231G>A		intron	N/A	ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73589 AN: 151846 Hom.: 18830 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.449 AC: 173259 AN: 385890 Hom.: 40409 Cov.: 3 AF XY: 0.458 AC XY: 92972 AN XY: 202870

African (AFR) AF: 0.636 AC: 7208 AN: 11334

American (AMR) AF: 0.288 AC: 4385 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 5187 AN: 11974

East Asian (EAS) AF: 0.448 AC: 11908 AN: 26600

South Asian (SAS) AF: 0.608 AC: 23253 AN: 38228

European-Finnish (FIN) AF: 0.423 AC: 9861 AN: 23328

Middle Eastern (MID) AF: 0.410 AC: 700 AN: 1708

European-Non Finnish (NFE) AF: 0.429 AC: 100941 AN: 235048

Other (OTH) AF: 0.437 AC: 9816 AN: 22456

GnomAD4 genome AF: 0.485 AC: 73653 AN: 151964 Hom.: 18849 Cov.: 32 AF XY: 0.485 AC XY: 35978 AN XY: 74238

African (AFR) AF: 0.636 AC: 26363 AN: 41470

American (AMR) AF: 0.335 AC: 5113 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1495 AN: 3466

East Asian (EAS) AF: 0.420 AC: 2173 AN: 5168

South Asian (SAS) AF: 0.616 AC: 2970 AN: 4818

European-Finnish (FIN) AF: 0.423 AC: 4433 AN: 10484

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29576 AN: 67956

Other (OTH) AF: 0.461 AC: 975 AN: 2116

Alfa AF: 0.451 Hom.: 53526

Bravo AF: 0.478

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.27
PhyloP100		-0.42
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: rs7916649; hg19: chr10-96534584;