Genetic Variant NM_207352.4:c.958C>T (chr4-186201313-C-T) – ACMG Classification: Pathogenic (11 pts)

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

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

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 3.80

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
CYP4V2	NM_207352.4 link	c.958C>T	p.Arg320*	stop_gained	Exon 7 of 11	ENST00000378802.5	NP_997235.3	Q6ZWL3-1
CYP4V2	XM_005262935.5 link	c.958C>T	p.Arg320*	stop_gained	Exon 7 of 11		XP_005262992.1
CYP4V2	XM_047450077.1 link	c.562C>T	p.Arg188*	stop_gained	Exon 5 of 9		XP_047306033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4V2	ENST00000378802.5 link	c.958C>T	p.Arg320*	stop_gained	Exon 7 of 11	1	NM_207352.4	ENSP00000368079.4		Q6ZWL3-1
CYP4V2	ENST00000507209.5 link	n.1799C>T		non_coding_transcript_exon_variant	Exon 3 of 6	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727236

show subpopulations

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.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Bietti crystalline corneoretinal dystrophy

Pathogenic:1

Apr 12, 2012

GeneReviews

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

- -

Retinitis pigmentosa

Pathogenic:1

Jun 01, 2021

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

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: case-control

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

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over