rs17880188

Variant names:

• chr10-94850180-G-A
• rs17880188
• NM_000769.4:c.1291+122G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-94850180-G-A
• chr10-94850180-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000769.4(CYP2C19):​c.1291+122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000296 in 1,012,914 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: CYP2C19 NM_000769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.817
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	NM_000769.4	MANE Select	c.1291+122G>A		intron	N/A	NP_000760.1	P33261

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C19	ENST00000371321.9	TSL:1 MANE Select	c.1291+122G>A		intron	N/A	ENSP00000360372.3	P33261
	ENSG00000276490	ENST00000464755.1	TSL:2	n.*1049+122G>A		intron	N/A	ENSP00000483243.1	A0A087X0B3
	CYP2C19	ENST00000883431.1		c.1315+122G>A		intron	N/A	ENSP00000553490.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000296 AC: 3 AN: 1012914 Hom.: 0 AF XY: 0.00000386 AC XY: 2 AN XY: 517754

African (AFR) AF: 0.00 AC: 0 AN: 24180

American (AMR) AF: 0.00 AC: 0 AN: 36230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21244

East Asian (EAS) AF: 0.00 AC: 0 AN: 36630

South Asian (SAS) AF: 0.0000428 AC: 3 AN: 70046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4406

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 732486

Other (OTH) AF: 0.00 AC: 0 AN: 45274

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.48
DANN	Benign	0.44
PhyloP100		-0.82

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: rs17880188; hg19: chr10-96609937;