rs2228113

chr1-59915940-T-C

Variant summary

Our verdict is Benign. Variant got -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. 16/21 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010835975).
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome 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 gnomad4_exome. There are 325 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2J2	NM_000775.4	c.371A>G	p.Asn124Ser	missense_variant, splice_region_variant	2/9	ENST00000371204.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2J2	ENST00000371204.4	c.371A>G	p.Asn124Ser	missense_variant, splice_region_variant	2/9	1	NM_000775.4	P1
CYP2J2	ENST00000468257.2	c.371A>G	p.Asn124Ser	missense_variant, splice_region_variant, NMD_transcript_variant	2/10	3
CYP2J2	ENST00000466095.5	c.371A>G	p.Asn124Ser	missense_variant, splice_region_variant, NMD_transcript_variant	2/8	3
CYP2J2	ENST00000469406.6	c.*132A>G		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	2/10	3

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

GnomAD3 exomes AF: 0.00104 AC: 260 AN: 249412 Hom.: 2 AF XY: 0.000764 AC XY: 103 AN XY: 134768

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 SAS exome AF: 0.0000998

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

Gnomad4 AFR exome AF: 0.0172

Gnomad4 AMR exome AF: 0.000812

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000140

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.00128

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

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000708 Hom.: 1

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 v4.3

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
MutationTaster	Benign	1.0	N
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2228113; hg19: chr1-60381612;