1-59904999-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0840

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 -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 GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2J2	NM_000775.4	c.1063G>A	p.Ala355Thr	missense_variant	7/9	ENST00000371204.4

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000993 AC: 151 AN: 152116 Hom.: 0 Cov.: 32

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.: 3 AF XY: 0.00226 AC XY: 306 AN XY: 135692

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.: 14 Cov.: 31 AF XY: 0.00143 AC XY: 1043 AN XY: 727090

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.: 0 Cov.: 32 AF XY: 0.00114 AC XY: 85 AN XY: 74426

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.: 0

Bravo AF: 0.000797

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.00185 AC: 224

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00147

EpiControl AF: 0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	6.4
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.10
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.0020	B
Vest4		0.035
MVP		0.52
MPC		0.12
ClinPred		0.023	T
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

Other links and lift over

dbSNP: rs144856672; hg19: chr1-60370671;