chr1-59917745-A-G

Variant names:

• chr1-59917745-A-G
• rs11572235
• NM_000775.4:c.211-1645T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000775.4(CYP2J2):​c.211-1645T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 152,256 control chromosomes in the GnomAD database, including 445 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 0.075 (445 hom., cov: 32)
• Consequence: CYP2J2 NM_000775.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2J2	NM_000775.4	c.211-1645T>C		intron_variant	Intron 1 of 8	ENST00000371204.4	NP_000766.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2J2	ENST00000371204.4	c.211-1645T>C		intron_variant	Intron 1 of 8	1	NM_000775.4	ENSP00000360247.3
CYP2J2	ENST00000466095.5	n.211-1645T>C		intron_variant	Intron 1 of 7	3		ENSP00000498084.1
CYP2J2	ENST00000468257.2	n.211-1645T>C		intron_variant	Intron 1 of 9	3		ENSP00000497807.1
CYP2J2	ENST00000469406.6	n.227-1645T>C		intron_variant	Intron 1 of 9	3		ENSP00000497732.1

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11369 AN: 152138 Hom.: 446 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0537

Gnomad EAS AF: 0.0445

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.0666

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

GnomAD4 genome AF: 0.0747 AC: 11373 AN: 152256 Hom.: 445 Cov.: 32 AF XY: 0.0724 AC XY: 5393 AN XY: 74452

African (AFR) AF: 0.108 AC: 4490 AN: 41526

American (AMR) AF: 0.0389 AC: 595 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0537 AC: 186 AN: 3466

East Asian (EAS) AF: 0.0442 AC: 229 AN: 5182

South Asian (SAS) AF: 0.0715 AC: 345 AN: 4824

European-Finnish (FIN) AF: 0.0550 AC: 583 AN: 10606

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0700 AC: 4762 AN: 68032

Other (OTH) AF: 0.0659 AC: 139 AN: 2110

Alfa AF: 0.0678 Hom.: 477

Bravo AF: 0.0736

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.60
PhyloP100		-1.3
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: rs11572235; hg19: chr1-60383417;