chr2-127052264-C-A

Position:

chr2-127052264-C-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_139343.3(BIN1):c.1362G>T(p.Gly454Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,572,668 control chromosomes in the GnomAD database, including 494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 40 hom., cov: 34)

Exomes 𝑓: 0.023 ( 454 hom. )

Consequence

BIN1
NM_139343.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.197

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 2-127052264-C-A is Benign according to our data. Variant chr2-127052264-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 158008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.197 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0504 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.1362G>T	p.Gly454Gly	synonymous_variant	15/19	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.1362G>T	p.Gly454Gly	synonymous_variant	15/19	1	NM_139343.3	ENSP00000316779.5		O00499-1

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2442

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00446

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0490

Gnomad FIN

AF:

0.0176

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0222

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0203

AC:

3632

AN:

178980

Hom.:

AF XY:

0.0229

AC XY:

2208

AN XY:

96378

show subpopulations

Gnomad AFR exome

AF:

0.00290

Gnomad AMR exome

AF:

0.00926

Gnomad ASJ exome

AF:

0.00890

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0510

Gnomad FIN exome

AF:

0.0171

Gnomad NFE exome

AF:

0.0226

Gnomad OTH exome

AF:

0.0185

GnomAD4 exome

AF:

0.0229

AC:

32552

AN:

1420316

Hom.:

454

Cov.:

AF XY:

0.0241

AC XY:

16959

AN XY:

702538

show subpopulations

Gnomad4 AFR exome

AF:

0.00294

Gnomad4 AMR exome

AF:

0.00947

Gnomad4 ASJ exome

AF:

0.00815

Gnomad4 EAS exome

AF:

0.0000798

Gnomad4 SAS exome

AF:

0.0517

Gnomad4 FIN exome

AF:

0.0166

Gnomad4 NFE exome

AF:

0.0234

Gnomad4 OTH exome

AF:

0.0211

GnomAD4 genome

AF:

0.0160

AC:

2441

AN:

152352

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1243

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00445

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0493

Gnomad4 FIN

AF:

0.0176

Gnomad4 NFE

AF:

0.0222

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0147

Hom.:

Bravo

AF:

0.0141

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 10, 2014	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 26, 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	PreventionGenetics, part of Exact Sciences	-	- -

Myopathy, centronuclear, 2

Benign:2

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 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

-0.37

CADD

Benign

7.6

DANN

Benign

0.72

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