rs61757320

Positions:

• chr10-95067487-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000371270.6(CYP2C8):​c.331+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,613,780 control chromosomes in the GnomAD database, including 4 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 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (4 hom.)
• Consequence: CYP2C8 ENST00000371270.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.331+42G>A		intron_variant		ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.121+42G>A		intron_variant			NP_001185782.1
CYP2C8	NM_001198854.1	c.26-130G>A		intron_variant			NP_001185783.1
CYP2C8	NM_001198855.1	c.121+42G>A		intron_variant			NP_001185784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.331+42G>A		intron_variant		1	NM_000770.3	ENSP00000360317	P1

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 268 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00312

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00186 AC: 467 AN: 250738 Hom.: 1 AF XY: 0.00170 AC XY: 231 AN XY: 135666

Gnomad AFR exome AF: 0.000437

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00166

Gnomad NFE exome AF: 0.00337

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.00267 AC: 3905 AN: 1461442 Hom.: 4 Cov.: 33 AF XY: 0.00262 AC XY: 1907 AN XY: 727048

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00204

Gnomad4 NFE exome AF: 0.00325

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.00176 AC: 268 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.00141 AC XY: 105 AN XY: 74504

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00312

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00201 Hom.: 0

Bravo AF: 0.00182

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.51
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs61757320; hg19: chr10-96827244;