rs138619320
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_014000.3(VCL):c.3066C>T(p.Ile1022Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,904 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014000.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VCL | NM_014000.3 | c.3066C>T | p.Ile1022Ile | synonymous_variant | Exon 20 of 22 | ENST00000211998.10 | NP_054706.1 | |
VCL | NM_003373.4 | c.2862C>T | p.Ile954Ile | synonymous_variant | Exon 19 of 21 | NP_003364.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 152022Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.000135 AC: 34AN: 251114Hom.: 0 AF XY: 0.0000958 AC XY: 13AN XY: 135710
GnomAD4 exome AF: 0.0000944 AC: 138AN: 1461882Hom.: 0 Cov.: 36 AF XY: 0.0000921 AC XY: 67AN XY: 727244
GnomAD4 genome AF: 0.0000855 AC: 13AN: 152022Hom.: 0 Cov.: 30 AF XY: 0.000108 AC XY: 8AN XY: 74262
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1W Uncertain:1Benign:1
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Benign:2
Ile1022Ile in exon 20 of VCL: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, and is not located wit hin the splice consensus sequence. It has been identified in 1/3738 African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs138619320). Ile1022Ile in exon 20 of VCL (rs138619320; allele frequency= 1/3738) ** -
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VCL-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at