rs10493270

Positions:

• chr1-59923002-G-A

Variant summary

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

The NM_000775.4(CYP2J2):​c.210+3535C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 152,256 control chromosomes in the GnomAD database, including 785 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 0.086 (785 hom., cov: 32)
• Consequence: CYP2J2 NM_000775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2J2	NM_000775.4	c.210+3535C>T		intron_variant		ENST00000371204.4	NP_000766.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2J2	ENST00000371204.4	c.210+3535C>T		intron_variant		1	NM_000775.4	ENSP00000360247	P1
CYP2J2	ENST00000466095.5	c.210+3535C>T		intron_variant, NMD_transcript_variant		3		ENSP00000498084
CYP2J2	ENST00000468257.2	c.210+3535C>T		intron_variant, NMD_transcript_variant		3		ENSP00000497807
CYP2J2	ENST00000469406.6	c.226+3519C>T		intron_variant, NMD_transcript_variant		3		ENSP00000497732

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 13136 AN: 152136 Hom.: 784 Cov.: 32

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0966

Gnomad OTH AF: 0.0830

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

GnomAD4 genome AF: 0.0863 AC: 13143 AN: 152256 Hom.: 785 Cov.: 32 AF XY: 0.0901 AC XY: 6707 AN XY: 74442

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.0965

Gnomad4 OTH AF: 0.0821

Alfa AF: 0.0971 Hom.: 1130

Bravo AF: 0.0873

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.37

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: rs10493270; hg19: chr1-60388674;