rs1934953

Variant names:

• chr10-95037713-C-T
• rs1934953
• NM_000770.3:c.1292-404G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-95037713-C-T
• chr10-95037713-C-A
• chr10-95037713-C-G

Variant summary

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

The NM_000770.3(CYP2C8):​c.1292-404G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,040 control chromosomes in the GnomAD database, including 36,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.69 (36575 hom., cov: 32)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.88
• Publications: 14 publications found

Genes affected

CYP2C8 (HGNC:2622): (cytochrome P450 family 2 subfamily C member 8) 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 its expression is induced by phenobarbital. The enzyme is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, benzo(a)pyrene, 7-ethyoxycoumarin, and the anti-cancer drug taxol. This gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000770.3. 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
	CYP2C8	NM_000770.3	MANE Select	c.1292-404G>A		intron	N/A	NP_000761.3	P10632-1
	CYP2C8	NM_001198853.1		c.1082-404G>A		intron	N/A	NP_001185782.1	P10632
	CYP2C8	NM_001198855.1		c.1082-404G>A		intron	N/A	NP_001185784.1	P10632

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C8	ENST00000371270.6	TSL:1 MANE Select	c.1292-404G>A		intron	N/A	ENSP00000360317.3	P10632-1
	CYP2C8	ENST00000854622.1		c.1373-404G>A		intron	N/A	ENSP00000524681.1
	CYP2C8	ENST00000854631.1		c.1328-404G>A		intron	N/A	ENSP00000524690.1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104304 AN: 151922 Hom.: 36523 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.687 AC: 104405 AN: 152040 Hom.: 36575 Cov.: 32 AF XY: 0.681 AC XY: 50604 AN XY: 74318

African (AFR) AF: 0.807 AC: 33473 AN: 41478

American (AMR) AF: 0.557 AC: 8508 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2450 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2385 AN: 5172

South Asian (SAS) AF: 0.669 AC: 3225 AN: 4818

European-Finnish (FIN) AF: 0.616 AC: 6495 AN: 10548

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45458 AN: 67962

Other (OTH) AF: 0.706 AC: 1491 AN: 2112

Alfa AF: 0.673 Hom.: 108031

Bravo AF: 0.684

Asia WGS AF: 0.607 AC: 2109 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.20
PhyloP100		-1.9
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: rs1934953; hg19: chr10-96797470;