rs72481904

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139343.3(BIN1):c.698+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,613,204 control chromosomes in the GnomAD database, including 105,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8320 hom., cov: 34)

Exomes 𝑓: 0.36 ( 96733 hom. )

Consequence

BIN1
NM_139343.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.06

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-127063923-T-C is Benign according to our data. Variant chr2-127063923-T-C is described in ClinVar as [Benign]. Clinvar id is 158017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-127063923-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIN1	NM_139343.3 linkuse as main transcript	c.698+10A>G		intron_variant		ENST00000316724.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIN1	ENST00000316724.10 linkuse as main transcript	c.698+10A>G		intron_variant		1	NM_139343.3		O00499-1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47850

AN:

151986

Hom.:

8303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.349

GnomAD3 exomes

AF:

0.374

AC:

93983

AN:

251006

Hom.:

18458

AF XY:

0.383

AC XY:

51987

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.429

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.402

Gnomad SAS exome

AF:

0.491

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.357

Gnomad OTH exome

AF:

0.383

GnomAD4 exome

AF:

0.360

AC:

525349

AN:

1461098

Hom.:

96733

Cov.:

AF XY:

0.364

AC XY:

264810

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.155

Gnomad4 AMR exome

AF:

0.424

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.352

Gnomad4 SAS exome

AF:

0.492

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.359

GnomAD4 genome

AF:

0.315

AC:

47893

AN:

152106

Hom.:

8320

Cov.:

AF XY:

0.322

AC XY:

23960

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.409

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.392

Gnomad4 SAS

AF:

0.492

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.351

Alfa

AF:

0.320

Hom.:

2449

Bravo

AF:

0.309

Asia WGS

AF:

0.430

AC:

1493

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 2016	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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	698+10A>G in intron 8 of BIN1: This variant is not expected to have clinical sig nificance because it is not located within the conserved splice consensus sequen ce. It has been identified in 34.9% (3002/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS; dbSNP rs72481904). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Myopathy, centronuclear, 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

0.87

Dann

Benign

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over