rs10493270

Variant names:

• chr1-59923002-G-A
• rs10493270
• NM_000775.4:c.210+3535C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000775.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2J2	NM_000775.4	MANE Select	c.210+3535C>T		intron	N/A	NP_000766.2
	CYP2J2	NR_134981.2		n.237+3535C>T		intron	N/A
	CYP2J2	NR_134982.2		n.237+3535C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2J2	ENST00000371204.4	TSL:1 MANE Select	c.210+3535C>T		intron	N/A	ENSP00000360247.3	P51589
	CYP2J2	ENST00000905907.1		c.201+3544C>T		intron	N/A	ENSP00000575966.1
	CYP2J2	ENST00000905910.1		c.210+3535C>T		intron	N/A	ENSP00000575969.1

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

African (AFR) AF: 0.0187 AC: 778 AN: 41568

American (AMR) AF: 0.148 AC: 2267 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.157 AC: 815 AN: 5182

South Asian (SAS) AF: 0.120 AC: 578 AN: 4822

European-Finnish (FIN) AF: 0.132 AC: 1399 AN: 10588

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0965 AC: 6566 AN: 68012

Other (OTH) AF: 0.0821 AC: 173 AN: 2106

Alfa AF: 0.0956 Hom.: 1551

Bravo AF: 0.0873

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.37
PhyloP100		0.019
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: rs10493270; hg19: chr1-60388674;