rs4388726

Positions:

• chr1-59893484-G-A
• chr1-59893484-G-C

Variant summary

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

The NM_000775.4(CYP2J2):​c.*167C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 503,482 control chromosomes in the GnomAD database, including 1,712 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 0.092 (796 hom., cov: 32)
  • Exomes 𝑓: 0.070 (916 hom.)
• Consequence: CYP2J2 NM_000775.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2J2	NM_000775.4	c.*167C>T		3_prime_UTR_variant	9/9	ENST00000371204.4	NP_000766.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2J2	ENST00000371204.4	c.*167C>T		3_prime_UTR_variant	9/9	1	NM_000775.4	ENSP00000360247	P1

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 14018 AN: 152066 Hom.: 792 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.0805

GnomAD4 exome AF: 0.0695 AC: 24419 AN: 351298 Hom.: 916 Cov.: 5 AF XY: 0.0694 AC XY: 12789 AN XY: 184286

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.0316

Gnomad4 ASJ exome AF: 0.0574

Gnomad4 EAS exome AF: 0.0562

Gnomad4 SAS exome AF: 0.0705

Gnomad4 FIN exome AF: 0.0622

Gnomad4 NFE exome AF: 0.0706

Gnomad4 OTH exome AF: 0.0775

GnomAD4 genome AF: 0.0923 AC: 14041 AN: 152184 Hom.: 796 Cov.: 32 AF XY: 0.0904 AC XY: 6727 AN XY: 74394

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0463

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0568

Gnomad4 SAS AF: 0.0764

Gnomad4 FIN AF: 0.0553

Gnomad4 NFE AF: 0.0711

Gnomad4 OTH AF: 0.0797

Alfa AF: 0.0708 Hom.: 760

Bravo AF: 0.0927

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.43

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: rs4388726; hg19: chr1-60359156; COSMIC: COSV64605455;