rs141119288
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_139343.3(BIN1):c.1292C>T(p.Pro431Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,587,120 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00061 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00050 ( 7 hom. )
Consequence
BIN1
NM_139343.3 missense
NM_139343.3 missense
Scores
3
13
Clinical Significance
Conservation
PhyloP100: 1.98
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006077647).
BP6
?
Variant 2-127052334-G-A is Benign according to our data. Variant chr2-127052334-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00061 (93/152386) while in subpopulation EAS AF= 0.0173 (90/5190). AF 95% confidence interval is 0.0144. There are 0 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 7 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIN1 | NM_139343.3 | c.1292C>T | p.Pro431Leu | missense_variant | 15/19 | ENST00000316724.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIN1 | ENST00000316724.10 | c.1292C>T | p.Pro431Leu | missense_variant | 15/19 | 1 | NM_139343.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000611 AC: 93AN: 152268Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00165 AC: 325AN: 197520Hom.: 4 AF XY: 0.00151 AC XY: 162AN XY: 107446
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GnomAD4 exome AF: 0.000502 AC: 720AN: 1434734Hom.: 7 Cov.: 31 AF XY: 0.000460 AC XY: 327AN XY: 711082
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GnomAD4 genome ? AF: 0.000610 AC: 93AN: 152386Hom.: 0 Cov.: 34 AF XY: 0.000671 AC XY: 50AN XY: 74510
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Myopathy, centronuclear, 2 Benign:2
Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 02, 2019 | This variant is associated with the following publications: (PMID: 24582639, 31182772) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;T;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D;D;N
REVEL
Benign
Sift
Benign
T;T;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;D;B;B
Vest4
MVP
MPC
0.29
ClinPred
T
GERP RS
Varity_R
gMVP
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