rs2228113

Variant names:

• chr1-59915940-T-C
• rs2228113
• NM_000775.4:c.371A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000775.4(CYP2J2):​c.371A>G​(p.Asn124Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000838 in 1,611,902 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0041 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (4 hom.)
• Consequence: CYP2J2 NM_000775.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001169
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 8 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 (MetaRNN=0.010835975).
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000497 (726/1459620) while in subpopulation AFR AF = 0.0172 (571/33256). AF 95% confidence interval is 0.016. There are 4 homozygotes in GnomAdExome4. There are 325 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2J2	NM_000775.4	MANE Select	c.371A>G	p.Asn124Ser	missense splice_region	Exon 2 of 9	NP_000766.2
	CYP2J2	NR_134981.2		n.398A>G		splice_region non_coding_transcript_exon	Exon 2 of 8
	CYP2J2	NR_134982.2		n.398A>G		splice_region non_coding_transcript_exon	Exon 2 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2J2	ENST00000371204.4	TSL:1 MANE Select	c.371A>G	p.Asn124Ser	missense splice_region	Exon 2 of 9	ENSP00000360247.3
	CYP2J2	ENST00000466095.5	TSL:3	n.371A>G		splice_region non_coding_transcript_exon	Exon 2 of 8	ENSP00000498084.1
	CYP2J2	ENST00000468257.2	TSL:3	n.371A>G		splice_region non_coding_transcript_exon	Exon 2 of 10	ENSP00000497807.1

Frequencies

GnomAD3 genomes AF: 0.00409 AC: 622 AN: 152164 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

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: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00104 AC: 260 AN: 249412 AF XY: 0.000764

Gnomad AFR exome AF: 0.0143

Gnomad AMR exome AF: 0.000558

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000497 AC: 726 AN: 1459620 Hom.: 4 Cov.: 31 AF XY: 0.000448 AC XY: 325 AN XY: 726032

African (AFR) AF: 0.0172 AC: 571 AN: 33256

American (AMR) AF: 0.000812 AC: 36 AN: 44324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00244 AC: 14 AN: 5744

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111182

Other (OTH) AF: 0.00128 AC: 77 AN: 60292

GnomAD4 genome AF: 0.00410 AC: 625 AN: 152282 Hom.: 7 Cov.: 32 AF XY: 0.00389 AC XY: 290 AN XY: 74460

African (AFR) AF: 0.0144 AC: 600 AN: 41552

American (AMR) AF: 0.000980 AC: 15 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68022

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00155 Hom.: 5

Bravo AF: 0.00462

ESP6500AA AF: 0.0143 AC: 63

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00126 AC: 153

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.2
DANN	Benign	0.55
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.77	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.54
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.084
Sift	Benign	0.74	T
Sift4G	Benign	0.89	T
Polyphen		0.011	B
Vest4		0.087
MVP		0.55
MPC		0.10
ClinPred		0.0027	T
GERP RS		-1.2
Varity_R		0.068
gMVP		0.12
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.070		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: rs2228113; hg19: chr1-60381612;