2-127059119-C-T

Position:

chr2-127059119-C-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.894G>A(p.Ser298Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,591,624 control chromosomes in the GnomAD database, including 2,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 300 hom., cov: 32)

Exomes 𝑓: 0.036 ( 2241 hom. )

Consequence

BIN1
NM_139343.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.21

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:

BIN1 (HGNC:):

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=-0.78).

BP6

Variant 2-127059119-C-T is Benign according to our data. Variant chr2-127059119-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 158022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-127059119-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 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.894G>A	p.Ser298Ser	synonymous_variant	11/19	ENST00000316724.10	NP_647593.1	O00499-1A0A024RAF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIN1	ENST00000316724.10 linkuse as main transcript	c.894G>A	p.Ser298Ser	synonymous_variant	11/19	1	NM_139343.3	ENSP00000316779.5		O00499-1

Frequencies

GnomAD3 genomes

AF:

0.0421

AC:

6389

AN:

151686

Hom.:

301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0900

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0221

Gnomad OTH

AF:

0.0412

GnomAD3 exomes

AF:

0.0732

AC:

15335

AN:

209514

Hom.:

1054

AF XY:

0.0703

AC XY:

7950

AN XY:

113050

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.0385

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.0853

Gnomad NFE exome

AF:

0.0219

Gnomad OTH exome

AF:

0.0468

GnomAD4 exome

AF:

0.0355

AC:

51154

AN:

1439820

Hom.:

2241

Cov.:

AF XY:

0.0374

AC XY:

26691

AN XY:

713978

show subpopulations

Gnomad4 AFR exome

AF:

0.0131

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.0382

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.0822

Gnomad4 NFE exome

AF:

0.0188

Gnomad4 OTH exome

AF:

0.0388

GnomAD4 genome

AF:

0.0421

AC:

6389

AN:

151804

Hom.:

300

Cov.:

AF XY:

0.0492

AC XY:

3646

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.0156

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0357

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.0900

Gnomad4 NFE

AF:

0.0221

Gnomad4 OTH

AF:

0.0389

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0429

Asia WGS

AF:

0.145

AC:

504

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 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. -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 20, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 28, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Ser298Ser in exon 11 of BIN1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 2.0% (169/8590) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs78936238). -

Myopathy, centronuclear, 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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	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

-0.78

CADD

Benign

0.85

DANN

Benign

0.75

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