chr1-59893484-G-A

Variant names:

• chr1-59893484-G-A
• rs4388726
• NM_000775.4:c.*167C>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.*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
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2J2	NM_000775.4	MANE Select	c.*167C>T		3_prime_UTR	Exon 9 of 9	NP_000766.2
	CYP2J2	NR_134981.2		n.1515C>T		non_coding_transcript_exon	Exon 8 of 8
	CYP2J2	NR_134982.2		n.1854C>T		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2J2	ENST00000371204.4	TSL:1 MANE Select	c.*167C>T		3_prime_UTR	Exon 9 of 9	ENSP00000360247.3
	CYP2J2	ENST00000466095.5	TSL:3	n.*420C>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000498084.1
	CYP2J2	ENST00000468257.2	TSL:3	n.*618C>T		non_coding_transcript_exon	Exon 10 of 10	ENSP00000497807.1

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

African (AFR) AF: 0.164 AC: 1634 AN: 9976

American (AMR) AF: 0.0316 AC: 536 AN: 16986

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 634 AN: 11038

East Asian (EAS) AF: 0.0562 AC: 1560 AN: 27770

South Asian (SAS) AF: 0.0705 AC: 993 AN: 14080

European-Finnish (FIN) AF: 0.0622 AC: 1817 AN: 29202

Middle Eastern (MID) AF: 0.0731 AC: 109 AN: 1492

European-Non Finnish (NFE) AF: 0.0706 AC: 15529 AN: 220018

Other (OTH) AF: 0.0775 AC: 1607 AN: 20736

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

African (AFR) AF: 0.165 AC: 6831 AN: 41508

American (AMR) AF: 0.0463 AC: 708 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3470

East Asian (EAS) AF: 0.0568 AC: 294 AN: 5178

South Asian (SAS) AF: 0.0764 AC: 369 AN: 4828

European-Finnish (FIN) AF: 0.0553 AC: 586 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0711 AC: 4837 AN: 68008

Other (OTH) AF: 0.0797 AC: 168 AN: 2108

Alfa AF: 0.0729 Hom.: 961

Bravo AF: 0.0927

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.43
PhyloP100		-0.20
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: rs4388726; hg19: chr1-60359156; COSMIC: COSV64605455;