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rs199476184

Positions:

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP3PP5

The NM_207352.4(CYP4V2):​c.1226-6_1235del variant causes a splice acceptor, coding sequence, 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).

Frequency

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

Consequence

CYP4V2
NM_207352.4 splice_acceptor, coding_sequence, 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1
?
    PVS1 - null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.113434725 fraction of the gene. Cryptic splice site detected, with MaxEntScore 4.4, offset of -4, new splice context is: aatgtattgactacttctAGttc. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP3
?
    PP3 - Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
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 UniProt
CYP4V2NM_207352.4 linkuse as main transcriptc.1226-6_1235del splice_acceptor_variant, coding_sequence_variant, intron_variant 10/11 ENST00000378802.5
CYP4V2XM_005262935.5 linkuse as main transcriptc.1226-9_1232del splice_acceptor_variant, coding_sequence_variant, intron_variant 10/11
CYP4V2XM_047450077.1 linkuse as main transcriptc.830-6_839del splice_acceptor_variant, coding_sequence_variant, intron_variant 8/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP4V2ENST00000378802.5 linkuse as main transcriptc.1226-6_1235del splice_acceptor_variant, coding_sequence_variant, intron_variant 10/111 NM_207352.4 P1Q6ZWL3-1
CYP4V2ENST00000502665.1 linkuse as main transcriptn.461-6_470del splice_acceptor_variant, non_coding_transcript_exon_variant, intron_variant 4/51
CYP4V2ENST00000507209.5 linkuse as main transcriptn.5924-6_5933del splice_acceptor_variant, non_coding_transcript_exon_variant, intron_variant 5/61
CYP4V2ENST00000513354.5 linkuse as main transcriptn.316-6_325del splice_acceptor_variant, non_coding_transcript_exon_variant, intron_variant 4/51

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00000657
AC:
1
AN:
152308
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
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 providedcurationGeneReviewsApr 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.

Other links and lift over

dbSNP: rs199476184; hg19: chr4-187130240; API