rs557276019
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_139343.3(BIN1):c.961G>A(p.Gly321Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000056 in 1,572,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_139343.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIN1 | NM_139343.3 | c.961G>A | p.Gly321Arg | missense_variant | 11/19 | ENST00000316724.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIN1 | ENST00000316724.10 | c.961G>A | p.Gly321Arg | missense_variant | 11/19 | 1 | NM_139343.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000212 AC: 32AN: 151298Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000327 AC: 6AN: 183546Hom.: 0 AF XY: 0.0000203 AC XY: 2AN XY: 98334
GnomAD4 exome AF: 0.0000394 AC: 56AN: 1420730Hom.: 0 Cov.: 32 AF XY: 0.0000398 AC XY: 28AN XY: 702758
GnomAD4 genome ? AF: 0.000211 AC: 32AN: 151418Hom.: 0 Cov.: 33 AF XY: 0.000230 AC XY: 17AN XY: 73942
ClinVar
Submissions by phenotype
Myopathy, centronuclear, 2 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 02, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 321 of the BIN1 protein (p.Gly321Arg). This variant is present in population databases (rs557276019, 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: 331052). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 24, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | The c.961G>A (p.G321R) alteration is located in exon 11 (coding exon 11) of the BIN1 gene. This alteration results from a G to A substitution at nucleotide position 961, causing the glycine (G) at amino acid position 321 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 07, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at