rs142523172

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

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.34
Variant links:
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]

Genome browser will be placed here

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
BIN1NM_139343.3 linkuse as main transcriptc.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
BIN1ENST00000316724.10 linkuse as main transcriptc.1611C>T p.Asp537= synonymous_variant 18/191 NM_139343.3 ENSP00000316779 O00499-1

Frequencies

GnomAD3 genomes
AF:
0.000959
AC:
146
AN:
152238
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00306
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000318
AC:
80
AN:
251410
Hom.:
1
AF XY:
0.000213
AC XY:
29
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00271
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00218
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000213
AC:
311
AN:
1461880
Hom.:
2
Cov.:
33
AF XY:
0.000190
AC XY:
138
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00317
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00268
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000998
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.000991
AC:
151
AN:
152356
Hom.:
1
Cov.:
34
AF XY:
0.00110
AC XY:
82
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.00317
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000765
Hom.:
0
Bravo
AF:
0.00101
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingEurofins Ntd Llc (ga)Apr 20, 2018- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 28, 2018- -
Myopathy, centronuclear, 2 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 12, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
CADD
Benign
1.1
DANN
Benign
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142523172; hg19: chr2-127808060; API