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
NM_207352.4 splice_acceptor, coding_sequence, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.94
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
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
?
Very rare variant in population databases, with high coverage;
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
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 | UniProt |
---|---|---|---|---|---|---|---|
CYP4V2 | NM_207352.4 | c.1226-6_1235del | splice_acceptor_variant, coding_sequence_variant, intron_variant | 10/11 | ENST00000378802.5 | ||
CYP4V2 | XM_005262935.5 | c.1226-9_1232del | splice_acceptor_variant, coding_sequence_variant, intron_variant | 10/11 | |||
CYP4V2 | XM_047450077.1 | c.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 |
---|---|---|---|---|---|---|---|---|---|
CYP4V2 | ENST00000378802.5 | c.1226-6_1235del | splice_acceptor_variant, coding_sequence_variant, intron_variant | 10/11 | 1 | NM_207352.4 | P1 | ||
CYP4V2 | ENST00000502665.1 | n.461-6_470del | splice_acceptor_variant, non_coding_transcript_exon_variant, intron_variant | 4/5 | 1 | ||||
CYP4V2 | ENST00000507209.5 | n.5924-6_5933del | splice_acceptor_variant, non_coding_transcript_exon_variant, intron_variant | 5/6 | 1 | ||||
CYP4V2 | ENST00000513354.5 | n.316-6_325del | splice_acceptor_variant, non_coding_transcript_exon_variant, intron_variant | 4/5 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74482
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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
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Name
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at