chr4-5748133-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_153717.3(EVC):c.940-15G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
EVC
NM_153717.3 splice_polypyrimidine_tract, intron
NM_153717.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.920
Genes affected
EVC (HGNC:3497): (EvC ciliary complex subunit 1) This gene encodes a protein containing a leucine zipper and a transmembrane domain. This gene has been implicated in both Ellis-van Creveld syndrome (EvC) and Weyers acrodental dysostosis. [provided by RefSeq, Jul 2008]
CRMP1 (HGNC:2365): (collapsin response mediator protein 1) This gene encodes a member of a family of cytosolic phosphoproteins expressed exclusively in the nervous system. The encoded protein is thought to be a part of the semaphorin signal transduction pathway implicated in semaphorin-induced growth cone collapse during neural development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 4-5748133-G-A is Benign according to our data. Variant chr4-5748133-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2927373.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EVC | NM_153717.3 | c.940-15G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000264956.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC | ENST00000264956.11 | c.940-15G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_153717.3 | P1 | |||
EVC | ENST00000509451.1 | c.940-15G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
CRMP1 | ENST00000506216.5 | n.1827C>T | non_coding_transcript_exon_variant | 13/13 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251432Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135900
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727226
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 02, 2023 | - - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at