10-95042980-G-A

Variant names:

• chr10-95042980-G-A
• rs11188150
• NM_000770.3:c.1059C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000770.3(CYP2C8):​c.1059C>T​(p.His353His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00553 in 1,614,018 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (191 hom.)
• Consequence: CYP2C8 NM_000770.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.775
• Publications: 8 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 10-95042980-G-A is Benign according to our data. Variant chr10-95042980-G-A is described in ClinVar as [Benign]. Clinvar id is 775289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.775 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0037 (564/152270) while in subpopulation SAS AF = 0.0498 (240/4822). AF 95% confidence interval is 0.0446. There are 11 homozygotes in GnomAd4. There are 332 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.1059C>T	p.His353His	synonymous_variant	Exon 7 of 9	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.849C>T	p.His283His	synonymous_variant	Exon 7 of 9		NP_001185782.1
CYP2C8	NM_001198855.1	c.849C>T	p.His283His	synonymous_variant	Exon 8 of 10		NP_001185784.1
CYP2C8	NM_001198854.1	c.753C>T	p.His251His	synonymous_variant	Exon 6 of 8		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.1059C>T	p.His353His	synonymous_variant	Exon 7 of 9	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 562 AN: 152152 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00279

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00882 AC: 2217 AN: 251478 AF XY: 0.0113

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.0172

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00323

Gnomad OTH exome AF: 0.00929

GnomAD4 exome AF: 0.00572 AC: 8355 AN: 1461748 Hom.: 191 Cov.: 32 AF XY: 0.00734 AC XY: 5334 AN XY: 727176

African (AFR) AF: 0.000448 AC: 15 AN: 33474

American (AMR) AF: 0.00197 AC: 88 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 461 AN: 26134

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39698

South Asian (SAS) AF: 0.0502 AC: 4334 AN: 86256

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53420

Middle Eastern (MID) AF: 0.0253 AC: 146 AN: 5768

European-Non Finnish (NFE) AF: 0.00254 AC: 2823 AN: 1111888

Other (OTH) AF: 0.00782 AC: 472 AN: 60386

GnomAD4 genome AF: 0.00370 AC: 564 AN: 152270 Hom.: 11 Cov.: 32 AF XY: 0.00446 AC XY: 332 AN XY: 74442

African (AFR) AF: 0.000505 AC: 21 AN: 41548

American (AMR) AF: 0.00196 AC: 30 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0498 AC: 240 AN: 4822

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00279 AC: 190 AN: 68022

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00406 Hom.: 21

Bravo AF: 0.00254

Asia WGS AF: 0.0190 AC: 65 AN: 3478

EpiCase AF: 0.00480

EpiControl AF: 0.00480

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.10
DANN	Benign	0.27
PhyloP100		-0.78
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: rs11188150; hg19: chr10-96802737; COSMIC: COSV104428898; COSMIC: COSV104428898;