chr2-127070022-C-T
Variant summary
Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1
The NM_139343.3(BIN1):c.384G>A(p.Thr128Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000401 in 1,614,128 control chromosomes in the GnomAD database, including 1 homozygotes. 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_139343.3 synonymous
Scores
Clinical Significance
Conservation
Publications
- myopathy, centronuclear, 2Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- centronuclear myopathyInheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
- autosomal dominant centronuclear myopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- autosomal recessive centronuclear myopathyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BIN1 | NM_139343.3 | c.384G>A | p.Thr128Thr | synonymous_variant | Exon 5 of 19 | ENST00000316724.10 | NP_647593.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00192 AC: 293AN: 152242Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.000605 AC: 152AN: 251276 AF XY: 0.000420 show subpopulations
GnomAD4 exome AF: 0.000242 AC: 354AN: 1461768Hom.: 1 Cov.: 31 AF XY: 0.000213 AC XY: 155AN XY: 727174 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00193 AC: 294AN: 152360Hom.: 0 Cov.: 33 AF XY: 0.00173 AC XY: 129AN XY: 74510 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Myopathy, centronuclear, 2 Uncertain:1Benign:1
- -
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:1
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at