rs199476194

Positions:

• chr4-186201313-C-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_207352.4(CYP4V2):​c.958C>T​(p.Arg320*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000103 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: CYP4V2 NM_207352.4 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 3.80

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]

CYP4V2 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-186201313-C-T is Pathogenic according to our data. Variant chr4-186201313-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 39272.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-186201313-C-T is described in Lovd as [Pathogenic]. Variant chr4-186201313-C-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4V2	NM_207352.4	c.958C>T	p.Arg320*	stop_gained	7/11	ENST00000378802.5	NP_997235.3
CYP4V2	XM_005262935.5	c.958C>T	p.Arg320*	stop_gained	7/11		XP_005262992.1
CYP4V2	XM_047450077.1	c.562C>T	p.Arg188*	stop_gained	5/9		XP_047306033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4V2	ENST00000378802.5	c.958C>T	p.Arg320*	stop_gained	7/11	1	NM_207352.4	ENSP00000368079.4
CYP4V2	ENST00000507209.5	n.1799C>T		non_coding_transcript_exon_variant	3/6	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461876 Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Bietti crystalline corneoretinal dystrophy Pathogenic:1

Pathogenic, no assertion criteria provided

curation

GeneReviews

Apr 12, 2012

- -

Retinitis pigmentosa Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

The Key Laboratory for Human Disease Gene Study of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital

Jun 01, 2021

It provides a new screening target for prenatal diagnosis of retinitis pigmentosa. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.99	D
Vest4		0.77
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs199476194; hg19: chr4-187122467;