rs1060743

Positions:

chr2-127068957-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_139343.3(BIN1):c.486T>C(p.Thr162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,613,848 control chromosomes in the GnomAD database, including 79,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7058 hom., cov: 34)

Exomes 𝑓: 0.31 ( 72648 hom. )

Consequence

BIN1
NM_139343.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.58

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 -21 ACMG points.

BP4

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

BP6

Variant 2-127068957-A-G is Benign according to our data. Variant chr2-127068957-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 158015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-127068957-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIN1	NM_139343.3 linkuse as main transcript	c.486T>C	p.Thr162=	synonymous_variant	6/19	ENST00000316724.10	NP_647593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIN1	ENST00000316724.10 linkuse as main transcript	c.486T>C	p.Thr162=	synonymous_variant	6/19	1	NM_139343.3	ENSP00000316779		O00499-1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45238

AN:

152000

Hom.:

7047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.304

GnomAD3 exomes

AF:

0.337

AC:

84816

AN:

251346

Hom.:

14948

AF XY:

0.342

AC XY:

46419

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.441

Gnomad SAS exome

AF:

0.446

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.311

AC:

455011

AN:

1461728

Hom.:

72648

Cov.:

AF XY:

0.315

AC XY:

229265

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.389

Gnomad4 ASJ exome

AF:

0.282

Gnomad4 EAS exome

AF:

0.378

Gnomad4 SAS exome

AF:

0.436

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.298

AC:

45280

AN:

152120

Hom.:

7058

Cov.:

AF XY:

0.303

AC XY:

22513

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.243

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.431

Gnomad4 SAS

AF:

0.448

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.300

Alfa

AF:

0.304

Hom.:

15590

Bravo

AF:

0.299

Asia WGS

AF:

0.445

AC:

1546

AN:

3478

EpiCase

AF:

0.297

EpiControl

AF:

0.299

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 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, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Thr162Thr in exon 6 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 29.0% (2498/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1060743). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -

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	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.062

DANN

Benign

0.52

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