1-59893663-A-T

Variant names:

• chr1-59893663-A-T
• rs2228114
• NM_000775.4:c.1497T>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000775.4(CYP2J2):​c.1497T>A​(p.Val499Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000756 in 1,605,662 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00043 (4 hom.)
• Consequence: CYP2J2 NM_000775.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.630
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 1-59893663-A-T is Benign according to our data. Variant chr1-59893663-A-T is described in ClinVar as Benign. ClinVar VariationId is 711960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.63 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000425 (618/1453360) while in subpopulation AFR AF = 0.0161 (535/33160). AF 95% confidence interval is 0.015. There are 4 homozygotes in GnomAdExome4. There are 255 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2J2	NM_000775.4	MANE Select	c.1497T>A	p.Val499Val	synonymous	Exon 9 of 9	NP_000766.2
	CYP2J2	NR_134981.2		n.1336T>A		non_coding_transcript_exon	Exon 8 of 8
	CYP2J2	NR_134982.2		n.1675T>A		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2J2	ENST00000371204.4	TSL:1 MANE Select	c.1497T>A	p.Val499Val	synonymous	Exon 9 of 9	ENSP00000360247.3	P51589
	CYP2J2	ENST00000905907.1		c.1488T>A	p.Val496Val	synonymous	Exon 9 of 9	ENSP00000575966.1
	CYP2J2	ENST00000905910.1		c.1410T>A	p.Val470Val	synonymous	Exon 9 of 9	ENSP00000575969.1

Frequencies

GnomAD3 genomes AF: 0.00392 AC: 596 AN: 152184 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00112 AC: 274 AN: 245400 AF XY: 0.000830

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.000863

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.000340

GnomAD4 exome AF: 0.000425 AC: 618 AN: 1453360 Hom.: 4 Cov.: 30 AF XY: 0.000353 AC XY: 255 AN XY: 722438

African (AFR) AF: 0.0161 AC: 535 AN: 33160

American (AMR) AF: 0.000830 AC: 36 AN: 43362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108530

Other (OTH) AF: 0.000733 AC: 44 AN: 60062

GnomAD4 genome AF: 0.00391 AC: 596 AN: 152302 Hom.: 2 Cov.: 33 AF XY: 0.00372 AC XY: 277 AN XY: 74472

African (AFR) AF: 0.0140 AC: 580 AN: 41570

American (AMR) AF: 0.000850 AC: 13 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000574 Hom.: 0

Bravo AF: 0.00443

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.4
DANN	Benign	0.58
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism

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: rs2228114; hg19: chr1-60359335;