Variant rs199476184 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_207352.4(CYP4V2):c.1226-6_1235delTGACAGCAGGTTACAG(p.Ala409fs) variant causes a frameshift, splice acceptor, splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,308 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CYP4V2
NM_207352.4 frameshift, splice_acceptor, splice_region, intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.94

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:

ENSG00000290316 (HGNC:):

ENSG00000290316 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 4-186209086-TTGACAGCAGGTTACAG-T is Pathogenic according to our data. Variant chr4-186209086-TTGACAGCAGGTTACAG-T is described in ClinVar as [Pathogenic]. Clinvar id is 39255.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-186209086-TTGACAGCAGGTTACAG-T is described in Lovd as [Likely_pathogenic]. Variant chr4-186209086-TTGACAGCAGGTTACAG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4V2	NM_207352.4 linkuse as main transcript	c.1226-6_1235delTGACAGCAGGTTACAG	p.Ala409fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	10/11	ENST00000378802.5	NP_997235.3	Q6ZWL3-1
CYP4V2	XM_005262935.5 linkuse as main transcript	c.1226-9_1232delTGACAGCAGGTTACAG	p.Gly409fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	10/11		XP_005262992.1
CYP4V2	XM_047450077.1 linkuse as main transcript	c.830-6_839delTGACAGCAGGTTACAG	p.Ala277fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	8/9		XP_047306033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4V2	ENST00000378802.5 linkuse as main transcript	c.1226-6_1235delTGACAGCAGGTTACAG	p.Ala409fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	10/11	1	NM_207352.4	ENSP00000368079.4		Q6ZWL3-1
ENSG00000290316	ENST00000511608.5 linkuse as main transcript	c.20-6_29delTGACAGCAGGTTACAG	p.Ala7fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	2/15	5		ENSP00000426629.1		H0YAC1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Bietti crystalline corneoretinal dystrophy

Pathogenic:1

Pathogenic, no assertion criteria provided

curation

GeneReviews

Apr 12, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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