Variant chr2-127050540-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_139343.3(BIN1):c.1573-18G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 1,613,712 control chromosomes in the GnomAD database, including 2,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 344 hom., cov: 34)

Exomes 𝑓: 0.037 ( 2479 hom. )

Consequence

BIN1
NM_139343.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.32

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=-1.02).

BP6

Variant 2-127050540-C-G is Benign according to our data. Variant chr2-127050540-C-G is described in ClinVar as [Benign]. Clinvar id is 262474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-127050540-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 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.1573-18G>C		intron_variant		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.1573-18G>C		intron_variant		1	NM_139343.3	ENSP00000316779		O00499-1

Frequencies

GnomAD3 genomes

AF:

0.0497

AC:

7562

AN:

152226

Hom.:

343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0907

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0221

Gnomad OTH

AF:

0.0459

GnomAD3 exomes

AF:

0.0754

AC:

18920

AN:

250800

Hom.:

1309

AF XY:

0.0725

AC XY:

9832

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.0402

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.0390

Gnomad EAS exome

AF:

0.144

Gnomad SAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.0883

Gnomad NFE exome

AF:

0.0231

Gnomad OTH exome

AF:

0.0516

GnomAD4 exome

AF:

0.0373

AC:

54474

AN:

1461368

Hom.:

2479

Cov.:

AF XY:

0.0391

AC XY:

28406

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.0396

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.0388

Gnomad4 EAS exome

AF:

0.140

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0834

Gnomad4 NFE exome

AF:

0.0189

Gnomad4 OTH exome

AF:

0.0412

GnomAD4 genome

AF:

0.0497

AC:

7570

AN:

152344

Hom.:

344

Cov.:

AF XY:

0.0563

AC XY:

4195

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0415

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.0366

Gnomad4 EAS

AF:

0.157

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.0907

Gnomad4 NFE

AF:

0.0222

Gnomad4 OTH

AF:

0.0436

Alfa

AF:

0.0179

Hom.:

Bravo

AF:

0.0514

Asia WGS

AF:

0.147

AC:

511

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Myopathy, centronuclear, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.17

DANN

Benign

0.38

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