rs1057911

chr10-94988980-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_000771.4(CYP2C9):c.1425A>T(p.Gly475=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 1,613,872 control chromosomes in the GnomAD database, including 3,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.050 (245 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3463 hom.)
• Consequence: CYP2C9 NM_000771.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

Genes affected

CYP2C9 (HGNC:2623): (cytochrome P450 family 2 subfamily C member 9) 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 rifampin. The enzyme is known to metabolize many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin. Studies identifying individuals who are poor metabolizers of phenytoin and tolbutamide suggest that this gene is polymorphic. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-94988980-A-T is Benign according to our data. Variant chr10-94988980-A-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-2.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C9	NM_000771.4	c.1425A>T	p.Gly475=	synonymous_variant	9/9	ENST00000260682.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C9	ENST00000260682.8	c.1425A>T	p.Gly475=	synonymous_variant	9/9	1	NM_000771.4	P1
CYP2C9	ENST00000643112.1	c.*434A>T		3_prime_UTR_variant, NMD_transcript_variant	8/8

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7560 AN: 152082 Hom.: 246 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0493

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.0531

GnomAD3 exomes AF: 0.0631 AC: 15870 AN: 251376 Hom.: 665 AF XY: 0.0683 AC XY: 9272 AN XY: 135850

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.0380

Gnomad ASJ exome AF: 0.0840

Gnomad EAS exome AF: 0.0337

Gnomad SAS exome AF: 0.110

Gnomad FIN exome AF: 0.0626

Gnomad NFE exome AF: 0.0684

Gnomad OTH exome AF: 0.0633

GnomAD4 exome AF: 0.0649 AC: 94874 AN: 1461672 Hom.: 3463 Cov.: 33 AF XY: 0.0662 AC XY: 48160 AN XY: 727152

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.0395

Gnomad4 ASJ exome AF: 0.0833

Gnomad4 EAS exome AF: 0.0301

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0627

Gnomad4 NFE exome AF: 0.0648

Gnomad4 OTH exome AF: 0.0645

GnomAD4 genome AF: 0.0496 AC: 7554 AN: 152200 Hom.: 245 Cov.: 32 AF XY: 0.0502 AC XY: 3736 AN XY: 74398

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.0492

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.0317

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0562

Gnomad4 NFE AF: 0.0663

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0647 Hom.: 196

Bravo AF: 0.0465

Asia WGS AF: 0.0770 AC: 267 AN: 3478

EpiCase AF: 0.0713

EpiControl AF: 0.0737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.23
Dann	Benign	0.46

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: rs1057911; hg19: chr10-96748737;