2-127059167-G-T

Position:

chr2-127059167-G-T

Variant summary

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

The NM_139343.3(BIN1):c.858-12C>A variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001381

Clinical Significance

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

Conservation

PhyloP100: -0.0720

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=-0.81).

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. Variant chr2-127059167-G-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
BIN1	NM_139343.3 linkuse as main transcript	c.858-12C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000316724.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIN1	ENST00000316724.10 linkuse as main transcript	c.858-12C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_139343.3		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

GnomAD3 exomes

AF:

0.176

AC:

30060

AN:

170668

Hom.:

2786

AF XY:

0.179

AC XY:

16337

AN XY:

91240

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 SAS exome

AF:

0.196

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

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.108

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.106

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.215

Gnomad4 NFE exome

AF:

0.197

Gnomad4 OTH exome

AF:

0.183

GnomAD4 genome

AF:

0.199

AC:

30236

AN:

151772

Hom.:

3166

Cov.:

AF XY:

0.198

AC XY:

14707

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.247

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.219

Gnomad4 NFE

AF:

0.196

Gnomad4 OTH

AF:

0.160

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 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	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 07, 2016	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -

Myopathy, centronuclear, 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
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. -

not provided

Benign:1

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

1.4

DANN

Benign

0.71

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

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