2-127048471-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting
The NM_139343.3(BIN1):c.*55G>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 0.0000103 in 1,359,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
BIN1
NM_139343.3 3_prime_UTR
NM_139343.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.95
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 was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BS1
Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000103 (14/1359456) while in subpopulation MID AF = 0.00072 (4/5554). AF 95% confidence interval is 0.000245. There are 0 homozygotes in GnomAdExome4. There are 10 alleles in the male GnomAdExome4 subpopulation. Median coverage is 21. This position FAILED quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| BIN1 | NM_139343.3 | c.*55G>A | 3_prime_UTR_variant | Exon 19 of 19 | ENST00000316724.10 | NP_647593.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.0000103 AC: 14AN: 1359456Hom.: 0 Cov.: 21 AF XY: 0.0000147 AC XY: 10AN XY: 681762 show subpopulations
GnomAD4 exome
AF:
AC:
14
AN:
1359456
Hom.:
Cov.:
21
AF XY:
AC XY:
10
AN XY:
681762
Gnomad4 AFR exome
AF:
AC:
2
AN:
31086
Gnomad4 AMR exome
AF:
AC:
0
AN:
44086
Gnomad4 ASJ exome
AF:
AC:
0
AN:
25440
Gnomad4 EAS exome
AF:
AC:
0
AN:
39124
Gnomad4 SAS exome
AF:
AC:
1
AN:
84290
Gnomad4 FIN exome
AF:
AC:
0
AN:
51910
Gnomad4 NFE exome
AF:
AC:
5
AN:
1021034
Gnomad4 Remaining exome
AF:
AC:
2
AN:
56932
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Myopathy, centronuclear, 2 Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at