1-59901568-T-C

Position:

• chr1-59901568-T-C

Variant summary

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

The NM_000775.4(CYP2J2):​c.1192-465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,056 control chromosomes in the GnomAD database, including 4,852 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 0.22 (4852 hom., cov: 32)
• Consequence: CYP2J2 NM_000775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.85

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2J2	NM_000775.4	c.1192-465A>G		intron_variant		ENST00000371204.4	NP_000766.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2J2	ENST00000371204.4	c.1192-465A>G		intron_variant		1	NM_000775.4	ENSP00000360247	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34107 AN: 151938 Hom.: 4835 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.225 AC: 34167 AN: 152056 Hom.: 4852 Cov.: 32 AF XY: 0.222 AC XY: 16509 AN XY: 74352

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.0870

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.0984

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.181

Alfa AF: 0.159 Hom.: 2142

Bravo AF: 0.232

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.046
DANN	Benign	0.75

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: rs2280275; hg19: chr1-60367240;