rs1137845

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_139343.3(BIN1):c.714C>T(p.Tyr238Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 1,613,502 control chromosomes in the GnomAD database, including 3,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 350 hom., cov: 33)

Exomes 𝑓: 0.045 ( 3058 hom. )

Consequence

BIN1
NM_139343.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.07

Publications

10 publications found

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]

BIN1 Gene-Disease associations (from GenCC):

myopathy, centronuclear, 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
centronuclear myopathy
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant centronuclear myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive centronuclear myopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-127063631-G-A is Benign according to our data. Variant chr2-127063631-G-A is described in ClinVar as [Benign]. Clinvar id is 158018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIN1	NM_139343.3 link	c.714C>T	p.Tyr238Tyr	synonymous_variant	Exon 9 of 19	ENST00000316724.10	NP_647593.1	O00499-1A0A024RAF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIN1	ENST00000316724.10 link	c.714C>T	p.Tyr238Tyr	synonymous_variant	Exon 9 of 19	1	NM_139343.3	ENSP00000316779.5		O00499-1

Frequencies

GnomAD3 genomes

AF:

0.0486

AC:

7396

AN:

152130

Hom.:

351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.0919

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0296

Gnomad OTH

AF:

0.0449

GnomAD2 exomes

AF:

0.0823

AC:

20566

AN:

249820

AF XY:

0.0813

show subpopulations

Gnomad AFR exome

AF:

0.0178

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.0532

Gnomad EAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.0890

Gnomad NFE exome

AF:

0.0302

Gnomad OTH exome

AF:

0.0592

GnomAD4 exome

AF:

0.0450

AC:

65730

AN:

1461254

Hom.:

3058

Cov.:

AF XY:

0.0476

AC XY:

34608

AN XY:

726918

show subpopulations

African (AFR)

AF:

0.0170

AC:

569

AN:

33474

American (AMR)

AF:

0.192

AC:

8555

AN:

44520

Ashkenazi Jewish (ASJ)

AF:

0.0518

AC:

1354

AN:

26120

East Asian (EAS)

AF:

0.138

AC:

5492

AN:

39684

South Asian (SAS)

AF:

0.144

AC:

12411

AN:

86150

European-Finnish (FIN)

AF:

0.0846

AC:

4512

AN:

53346

Middle Eastern (MID)

AF:

0.0487

AC:

281

AN:

5768

European-Non Finnish (NFE)

AF:

0.0267

AC:

29679

AN:

1111806

Other (OTH)

AF:

0.0476

AC:

2877

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

3580

7160

10741

14321

17901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0486

AC:

7402

AN:

152248

Hom.:

350

Cov.:

AF XY:

0.0559

AC XY:

4159

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0193

AC:

804

AN:

41554

American (AMR)

AF:

0.115

AC:

1764

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0539

AC:

187

AN:

3470

East Asian (EAS)

AF:

0.154

AC:

795

AN:

5164

South Asian (SAS)

AF:

0.157

AC:

759

AN:

4820

European-Finnish (FIN)

AF:

0.0919

AC:

973

AN:

10592

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0296

AC:

2012

AN:

68030

Other (OTH)

AF:

0.0426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

350

700

1051

1401

1751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0385

Hom.:

266

Bravo

AF:

0.0487

Asia WGS

AF:

0.159

AC:

551

AN:

3478

EpiCase

AF:

0.0320

EpiControl

AF:

0.0296

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Tyr238Tyr in exon 9 of BIN1: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 2.9% (248/8600) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs1137845). -

Myopathy, centronuclear, 2

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.14

(source)

DANN

Benign

0.51

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1137845

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over