rs1268605937
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014000.3(VCL):c.3258+4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,430,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_014000.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.3258+4T>C | splice_region_variant, intron_variant | ENST00000211998.10 | NP_054706.1 | |||
VCL | NM_003373.4 | c.3054+4T>C | splice_region_variant, intron_variant | NP_003364.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VCL | ENST00000211998.10 | c.3258+4T>C | splice_region_variant, intron_variant | 1 | NM_014000.3 | ENSP00000211998.5 | ||||
VCL | ENST00000372755.7 | c.3054+4T>C | splice_region_variant, intron_variant | 1 | ENSP00000361841.3 | |||||
VCL | ENST00000623461.3 | n.5857+4T>C | splice_region_variant, intron_variant | 1 | ||||||
VCL | ENST00000624354.3 | n.*3013+4T>C | splice_region_variant, intron_variant | 2 | ENSP00000485551.1 |
Frequencies
GnomAD3 genomes Cov.: 29
GnomAD3 exomes AF: 0.0000203 AC: 4AN: 196946Hom.: 0 AF XY: 0.0000287 AC XY: 3AN XY: 104686
GnomAD4 exome AF: 0.00000280 AC: 4AN: 1430074Hom.: 0 Cov.: 31 AF XY: 0.00000424 AC XY: 3AN XY: 708240
GnomAD4 genome Cov.: 29
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1W Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 07, 2019 | This sequence change falls in intron 21 of the VCL gene. It does not directly change the encoded amino acid sequence of the VCL protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with VCL-related disease. ClinVar contains an entry for this variant (Variation ID: 536717). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at