XM_047447499.1:c.-99-10722G>T

Variant names:

• chr1-59926822-C-A
• rs890293
• XM_047447499.1:c.-99-10722G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047447499.1(CYP2J2):​c.-99-10722G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,366,918 control chromosomes in the GnomAD database, including 3,774 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 0.084 (641 hom., cov: 32)
  • Exomes 𝑓: 0.069 (3133 hom.)
• Consequence: CYP2J2 XM_047447499.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 92 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371204.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2J2	NM_000775.4	MANE Select	c.-76G>T		upstream_gene	N/A	NP_000766.2
	CYP2J2	NR_134981.2		n.-49G>T		upstream_gene	N/A
	CYP2J2	NR_134982.2		n.-49G>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2J2	ENST00000371204.4	TSL:1 MANE Select	c.-76G>T		upstream_gene	N/A	ENSP00000360247.3
	CYP2J2	ENST00000466095.5	TSL:3	n.-76G>T		upstream_gene	N/A	ENSP00000498084.1
	CYP2J2	ENST00000468257.2	TSL:3	n.-76G>T		upstream_gene	N/A	ENSP00000497807.1

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12846 AN: 152160 Hom.: 641 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0544

Gnomad EAS AF: 0.0443

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0731

GnomAD4 exome AF: 0.0692 AC: 84067 AN: 1214640 Hom.: 3133 Cov.: 17 AF XY: 0.0689 AC XY: 41642 AN XY: 604308

African (AFR) AF: 0.140 AC: 3912 AN: 27852

American (AMR) AF: 0.0307 AC: 1054 AN: 34320

Ashkenazi Jewish (ASJ) AF: 0.0554 AC: 1283 AN: 23168

East Asian (EAS) AF: 0.0468 AC: 1624 AN: 34668

South Asian (SAS) AF: 0.0620 AC: 4632 AN: 74652

European-Finnish (FIN) AF: 0.0609 AC: 2797 AN: 45930

Middle Eastern (MID) AF: 0.0672 AC: 249 AN: 3706

European-Non Finnish (NFE) AF: 0.0704 AC: 64658 AN: 918880

Other (OTH) AF: 0.0750 AC: 3858 AN: 51464

GnomAD4 genome AF: 0.0844 AC: 12850 AN: 152278 Hom.: 641 Cov.: 32 AF XY: 0.0819 AC XY: 6099 AN XY: 74472

African (AFR) AF: 0.142 AC: 5893 AN: 41546

American (AMR) AF: 0.0423 AC: 647 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0544 AC: 189 AN: 3472

East Asian (EAS) AF: 0.0440 AC: 228 AN: 5176

South Asian (SAS) AF: 0.0703 AC: 339 AN: 4822

European-Finnish (FIN) AF: 0.0551 AC: 585 AN: 10618

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0701 AC: 4771 AN: 68022

Other (OTH) AF: 0.0723 AC: 153 AN: 2116

Alfa AF: 0.0745 Hom.: 71

Bravo AF: 0.0849

Asia WGS AF: 0.0640 AC: 220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.3
DANN	Benign	0.81
PhyloP100		-1.2
PromoterAI		-0.039	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs890293; hg19: chr1-60392494;