rs746346952
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_139343.3(BIN1):c.1412C>T(p.Ala471Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A471A) has been classified as Likely benign.
Frequency
Consequence
NM_139343.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIN1 | NM_139343.3 | c.1412C>T | p.Ala471Val | missense_variant | 16/19 | ENST00000316724.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIN1 | ENST00000316724.10 | c.1412C>T | p.Ala471Val | missense_variant | 16/19 | 1 | NM_139343.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152176Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249722Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135344
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461344Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 726992
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74332
ClinVar
Submissions by phenotype
Myopathy, centronuclear, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 12, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 471 of the BIN1 protein (p.Ala471Val). This variant is present in population databases (rs746346952, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BIN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 461704). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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