1-59915912-C-T

Variant names:

• chr1-59915912-C-T
• rs3738474
• NM_000775.4:c.373+26G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000775.4(CYP2J2):​c.373+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0662 in 1,605,960 control chromosomes in the GnomAD database, including 3,765 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 0.049 (214 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3551 hom.)
• Consequence: CYP2J2 NM_000775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797

Genes affected

CYP2J2 (HGNC:2634): (cytochrome P450 family 2 subfamily J member 2) 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 is thought to be the predominant enzyme responsible for epoxidation of endogenous arachidonic acid in cardiac tissue. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2J2	NM_000775.4	c.373+26G>A		intron_variant	Intron 2 of 8	ENST00000371204.4	NP_000766.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2J2	ENST00000371204.4	c.373+26G>A		intron_variant	Intron 2 of 8	1	NM_000775.4	ENSP00000360247.3
CYP2J2	ENST00000466095.5	n.373+26G>A		intron_variant	Intron 2 of 7	3		ENSP00000498084.1
CYP2J2	ENST00000468257.2	n.373+26G>A		intron_variant	Intron 2 of 9	3		ENSP00000497807.1
CYP2J2	ENST00000469406.6	n.*134+26G>A		intron_variant	Intron 2 of 9	3		ENSP00000497732.1

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 7463 AN: 152118 Hom.: 215 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0324

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0433

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0483

GnomAD3 exomes AF: 0.0569 AC: 13984 AN: 245910 Hom.: 445 AF XY: 0.0589 AC XY: 7824 AN XY: 132824

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.0222

Gnomad ASJ exome AF: 0.0584

Gnomad EAS exome AF: 0.0502

Gnomad SAS exome AF: 0.0643

Gnomad FIN exome AF: 0.0605

Gnomad NFE exome AF: 0.0717

Gnomad OTH exome AF: 0.0590

GnomAD4 exome AF: 0.0680 AC: 98888 AN: 1453724 Hom.: 3551 Cov.: 30 AF XY: 0.0680 AC XY: 49161 AN XY: 722710

Gnomad4 AFR exome AF: 0.0132

Gnomad4 AMR exome AF: 0.0238

Gnomad4 ASJ exome AF: 0.0573

Gnomad4 EAS exome AF: 0.0465

Gnomad4 SAS exome AF: 0.0626

Gnomad4 FIN exome AF: 0.0613

Gnomad4 NFE exome AF: 0.0731

Gnomad4 OTH exome AF: 0.0690

GnomAD4 genome AF: 0.0490 AC: 7462 AN: 152236 Hom.: 214 Cov.: 32 AF XY: 0.0481 AC XY: 3577 AN XY: 74428

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.0324

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.0430

Gnomad4 SAS AF: 0.0711

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.0717

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0496 Hom.: 108

Bravo AF: 0.0443

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.61
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3738474; hg19: chr1-60381584; COSMIC: COSV64605648; COSMIC: COSV64605648;