rs587783346

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139343.3(BIN1):c.858-12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,564,704 control chromosomes in the GnomAD database, including 29,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3166 hom., cov: 31)

Exomes 𝑓: 0.19 ( 26706 hom. )

Consequence

BIN1
NM_139343.3 intron

Scores

Splicing: ADA: 0.001381

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.0720

Publications

6 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-127059167-G-T is Benign according to our data. Variant chr2-127059167-G-T is described in ClinVar as [Benign]. Clinvar id is 158020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIN1	NM_139343.3 link	c.858-12C>A		intron_variant	Intron 10 of 18	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.858-12C>A		intron_variant	Intron 10 of 18	1	NM_139343.3	ENSP00000316779.5		O00499-1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30211

AN:

151654

Hom.:

3162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.163

GnomAD2 exomes

AF:

0.176

AC:

30060

AN:

170668

AF XY:

0.179

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.193

AC:

272036

AN:

1412932

Hom.:

26706

Cov.:

AF XY:

0.191

AC XY:

133556

AN XY:

698274

show subpopulations

African (AFR)

AF:

0.250

AC:

8115

AN:

32456

American (AMR)

AF:

0.108

AC:

4043

AN:

37466

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

3861

AN:

25274

East Asian (EAS)

AF:

0.106

AC:

3963

AN:

37332

South Asian (SAS)

AF:

0.191

AC:

15314

AN:

80306

European-Finnish (FIN)

AF:

0.215

AC:

10439

AN:

48504

Middle Eastern (MID)

AF:

0.160

AC:

917

AN:

5716

European-Non Finnish (NFE)

AF:

0.197

AC:

214642

AN:

1087268

Other (OTH)

AF:

0.183

AC:

10742

AN:

58610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

12787

25575

38362

51150

63937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.199

AC:

30236

AN:

151772

Hom.:

3166

Cov.:

AF XY:

0.198

AC XY:

14707

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.247

AC:

10196

AN:

41322

American (AMR)

AF:

0.121

AC:

1851

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.152

AC:

529

AN:

3472

East Asian (EAS)

AF:

0.125

AC:

644

AN:

5140

South Asian (SAS)

AF:

0.189

AC:

908

AN:

4798

European-Finnish (FIN)

AF:

0.219

AC:

2313

AN:

10568

Middle Eastern (MID)

AF:

0.188

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.196

AC:

13281

AN:

67898

Other (OTH)

AF:

0.160

AC:

337

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1133

2265

3398

4530

5663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.188

Hom.:

584

Bravo

AF:

0.192

Asia WGS

AF:

0.166

AC:

579

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Apr 07, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 29, 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. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

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

858-12C>A in intron 10 of BIN1: This variant is not expected to have clinical si gnificance because it has been identified in 22.3% (978/4376) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs6720741). -

Myopathy, centronuclear, 2

Benign:3

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. -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.81

CADD

Benign

1.4

(source)

DANN

Benign

0.71

PhyloP100

-0.072

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.098

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

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

rs587783346

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