NM_207352.4:c.181G>A

Variant names:

• chr4-186192004-G-A
• rs119103285
• NM_207352.4:c.181G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_207352.4(CYP4V2):​c.181G>A​(p.Gly61Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYP4V2 NM_207352.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 4.77

Genes affected

CYP4V2 (HGNC:23198): (cytochrome P450 family 4 subfamily V member 2) This gene encodes a member of the cytochrome P450 hemethiolate protein superfamily which are involved in oxidizing various substrates in the metabolic pathway. It is implicated in the metabolism of fatty acid precursors into n-3 polyunsaturated fatty acids. Mutations in this gene result in Bietti crystalline corneoretinal dystrophy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.994
• PP5: Variant 4-186192004-G-A is Pathogenic according to our data. Variant chr4-186192004-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2190.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-186192004-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4V2	NM_207352.4	c.181G>A	p.Gly61Ser	missense_variant	Exon 1 of 11	ENST00000378802.5	NP_997235.3
CYP4V2	XM_005262935.5	c.181G>A	p.Gly61Ser	missense_variant	Exon 1 of 11		XP_005262992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4V2	ENST00000378802.5	c.181G>A	p.Gly61Ser	missense_variant	Exon 1 of 11	1	NM_207352.4	ENSP00000368079.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Bietti crystalline corneoretinal dystrophy Pathogenic:2

May 01, 2004

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Apr 12, 2012

GeneReviews

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.87	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Pathogenic	3.7	H
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Pathogenic	0.87
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.84
MutPred		0.97		Loss of sheet (P = 0.1907);
MVP		0.97
MPC		0.40
ClinPred		1.0	D
GERP RS		4.4
Varity_R		0.96
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs119103285; hg19: chr4-187113158;