2-127048444-G-T
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_139343.3(BIN1):c.*82C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,384,950 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0060 ( 10 hom., cov: 33)
Exomes 𝑓: 0.00065 ( 9 hom. )
Consequence
BIN1
NM_139343.3 3_prime_UTR
NM_139343.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.933
Genes affected
BIN1 (HGNC:1052): (bridging integrator 1) This gene encodes several isoforms of a nucleocytoplasmic adaptor protein, one of which was initially identified as a MYC-interacting protein with features of a tumor suppressor. Isoforms that are expressed in the central nervous system may be involved in synaptic vesicle endocytosis and may interact with dynamin, synaptojanin, endophilin, and clathrin. Isoforms that are expressed in muscle and ubiquitously expressed isoforms localize to the cytoplasm and nucleus and activate a caspase-independent apoptotic process. Studies in mouse suggest that this gene plays an important role in cardiac muscle development. Alternate splicing of the gene results in several transcript variants encoding different isoforms. Aberrant splice variants expressed in tumor cell lines have also been described. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 2-127048444-G-T is Benign according to our data. Variant chr2-127048444-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 892713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.006 (913/152244) while in subpopulation AFR AF= 0.0207 (861/41548). AF 95% confidence interval is 0.0196. There are 10 homozygotes in gnomad4. There are 442 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 10 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BIN1 | NM_139343.3 | c.*82C>A | 3_prime_UTR_variant | 19/19 | ENST00000316724.10 | NP_647593.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BIN1 | ENST00000316724.10 | c.*82C>A | 3_prime_UTR_variant | 19/19 | 1 | NM_139343.3 | ENSP00000316779 |
Frequencies
GnomAD3 genomes AF: 0.00596 AC: 906AN: 152126Hom.: 10 Cov.: 33
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GnomAD4 exome AF: 0.000646 AC: 796AN: 1232706Hom.: 9 Cov.: 17 AF XY: 0.000558 AC XY: 348AN XY: 623616
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GnomAD4 genome AF: 0.00600 AC: 913AN: 152244Hom.: 10 Cov.: 33 AF XY: 0.00594 AC XY: 442AN XY: 74440
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 22, 2019 | - - |
Myopathy, centronuclear, 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at