rs199476200

Variant names:

• chr4-186208931-A-C
• rs199476200
• NM_207352.4:c.1157A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-186208931-A-C
• chr4-186208931-A-G

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.1157A>C​(p.Lys386Thr) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: CYP4V2 NM_207352.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.30

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]

ENSG00000290316 (HGNC:):

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, 0.983
• PP5: Variant 4-186208931-A-C is Pathogenic according to our data. Variant chr4-186208931-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 39250.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4V2	NM_207352.4	c.1157A>C	p.Lys386Thr	missense_variant	Exon 9 of 11	ENST00000378802.5	NP_997235.3
CYP4V2	XM_005262935.5	c.1157A>C	p.Lys386Thr	missense_variant	Exon 9 of 11		XP_005262992.1
CYP4V2	XM_047450077.1	c.761A>C	p.Lys254Thr	missense_variant	Exon 7 of 9		XP_047306033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4V2	ENST00000378802.5	c.1157A>C	p.Lys386Thr	missense_variant	Exon 9 of 11	1	NM_207352.4	ENSP00000368079.4
ENSG00000290316	ENST00000511608.5	c.-50A>C		upstream_gene_variant		5		ENSP00000426629.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Bietti crystalline corneoretinal dystrophy Pathogenic:1

Apr 12, 2012

GeneReviews

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Pathogenic	4.8	H
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.91
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.91		Loss of methylation at K386 (P = 0.0172);
MVP		0.98
MPC		0.44
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.94
gMVP		0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs199476200; hg19: chr4-187130085;