Variant 1-59904999-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000775.4(CYP2J2):c.1063G>A(p.Ala355Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,613,860 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 14 hom. )

Consequence

CYP2J2
NM_000775.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0840

Variant links:

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]

CYP2J2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077751577).

BP6

Variant 1-59904999-C-T is Benign according to our data. Variant chr1-59904999-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638850.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00117 (1709/1461626) while in subpopulation MID AF= 0.0184 (106/5766). AF 95% confidence interval is 0.0155. There are 14 homozygotes in gnomad4_exome. There are 1043 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2J2	NM_000775.4 linkuse as main transcript	c.1063G>A	p.Ala355Thr	missense_variant	7/9	ENST00000371204.4	NP_000766.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2J2	ENST00000371204.4 linkuse as main transcript	c.1063G>A	p.Ala355Thr	missense_variant	7/9	1	NM_000775.4	ENSP00000360247	P1

Frequencies

GnomAD3 genomes

AF:

0.000993

AC:

151

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00188

AC:

473

AN:

251050

Hom.:

AF XY:

0.00226

AC XY:

306

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00812

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00117

AC:

1709

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1043

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00853

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000617

Gnomad4 OTH exome

AF:

0.00172

GnomAD4 genome

AF:

0.00101

AC:

153

AN:

152234

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00853

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.000797

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00185

AC:

224

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

CYP2J2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

6.4

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.77

M_CAP

Benign

0.015

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

0.11

REVEL

Benign

0.10

Sift

Uncertain

0.024

Sift4G

Uncertain

0.0060

Polyphen

0.0020

Vest4

0.035

MVP

0.52

MPC

0.12

ClinPred

0.023

GERP RS

2.9

Varity_R

0.064

gMVP

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over