rs1891071

Variant names:

• chr10-95045614-C-T
• rs1891071
• NM_000770.3:c.961+196G>A

Variant summary

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

The NM_000770.3(CYP2C8):​c.961+196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,078 control chromosomes in the GnomAD database, including 31,892 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 0.64 (31892 hom., cov: 33)
• Consequence: CYP2C8 NM_000770.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.961+196G>A		intron_variant	Intron 6 of 8	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.751+196G>A		intron_variant	Intron 6 of 8		NP_001185782.1
CYP2C8	NM_001198855.1	c.751+196G>A		intron_variant	Intron 7 of 9		NP_001185784.1
CYP2C8	NM_001198854.1	c.655+196G>A		intron_variant	Intron 5 of 7		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.961+196G>A		intron_variant	Intron 6 of 8	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97320 AN: 151960 Hom.: 31851 Cov.: 33

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.640 AC: 97406 AN: 152078 Hom.: 31892 Cov.: 33 AF XY: 0.634 AC XY: 47175 AN XY: 74352

African (AFR) AF: 0.758 AC: 31471 AN: 41498

American (AMR) AF: 0.502 AC: 7665 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2250 AN: 3472

East Asian (EAS) AF: 0.431 AC: 2225 AN: 5164

South Asian (SAS) AF: 0.617 AC: 2980 AN: 4830

European-Finnish (FIN) AF: 0.582 AC: 6156 AN: 10574

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42394 AN: 67954

Other (OTH) AF: 0.653 AC: 1380 AN: 2112

Alfa AF: 0.628 Hom.: 50097

Bravo AF: 0.637

Asia WGS AF: 0.561 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.98
DANN	Benign	0.20
PhyloP100		-0.30
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: rs1891071; hg19: chr10-96805371;