rs142523172
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000316724.10(BIN1):c.1611C>T(p.Asp537=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000286 in 1,614,236 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00099 ( 1 hom., cov: 34)
Exomes 𝑓: 0.00021 ( 2 hom. )
Consequence
BIN1
ENST00000316724.10 synonymous
ENST00000316724.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.34
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 2-127050484-G-A is Benign according to our data. Variant chr2-127050484-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 461707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.34 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000991 (151/152356) while in subpopulation AFR AF= 0.00317 (132/41596). AF 95% confidence interval is 0.00273. There are 1 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BIN1 | NM_139343.3 | c.1611C>T | p.Asp537= | synonymous_variant | 18/19 | ENST00000316724.10 | NP_647593.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BIN1 | ENST00000316724.10 | c.1611C>T | p.Asp537= | synonymous_variant | 18/19 | 1 | NM_139343.3 | ENSP00000316779 |
Frequencies
GnomAD3 genomes AF: 0.000959 AC: 146AN: 152238Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.000318 AC: 80AN: 251410Hom.: 1 AF XY: 0.000213 AC XY: 29AN XY: 135904
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GnomAD4 exome AF: 0.000213 AC: 311AN: 1461880Hom.: 2 Cov.: 33 AF XY: 0.000190 AC XY: 138AN XY: 727242
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GnomAD4 genome AF: 0.000991 AC: 151AN: 152356Hom.: 1 Cov.: 34 AF XY: 0.00110 AC XY: 82AN XY: 74502
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 20, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 28, 2018 | - - |
Myopathy, centronuclear, 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 12, 2023 | - - |
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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at