rs67327804

Variant names:

Variant summary

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

The NM_139343.3(BIN1):c.412-25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,608,512 control chromosomes in the GnomAD database, including 86,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.33 ( 8602 hom., cov: 33)

Exomes 𝑓: 0.32 ( 78146 hom. )

Consequence

BIN1
NM_139343.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.796

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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-127069056-A-G is Benign according to our data. Variant chr2-127069056-A-G is described in ClinVar as [Benign]. Clinvar id is 678128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-127069056-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIN1	NM_139343.3 link	c.412-25T>C		intron_variant	Intron 5 of 18	ENST00000316724.10	NP_647593.1	O00499-1A0A024RAF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIN1	ENST00000316724.10 link	c.412-25T>C		intron_variant	Intron 5 of 18	1	NM_139343.3	ENSP00000316779.5		O00499-1

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50157

AN:

151948

Hom.:

8591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.402

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.0952

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.291

GnomAD3 exomes

AF:

0.300

AC:

74848

AN:

249172

Hom.:

12211

AF XY:

0.309

AC XY:

41736

AN XY:

134862

show subpopulations

Gnomad AFR exome

AF:

0.394

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.407

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.324

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.323

AC:

470415

AN:

1456446

Hom.:

78146

Cov.:

AF XY:

0.324

AC XY:

235113

AN XY:

724820

show subpopulations

Gnomad4 AFR exome

AF:

0.406

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.259

Gnomad4 EAS exome

AF:

0.0879

Gnomad4 SAS exome

AF:

0.405

Gnomad4 FIN exome

AF:

0.336

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.330

AC:

50203

AN:

152066

Hom.:

8602

Cov.:

AF XY:

0.329

AC XY:

24453

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.402

Gnomad4 AMR

AF:

0.230

Gnomad4 ASJ

AF:

0.266

Gnomad4 EAS

AF:

0.0960

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.336

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.295

Alfa

AF:

0.320

Hom.:

2088

Bravo

AF:

0.317

Asia WGS

AF:

0.258

AC:

900

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Myopathy, centronuclear, 2

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

DANN

Benign

0.54

BranchPoint Hunter

2.0

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