rs587783344

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_139343.3(BIN1):c.698+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,613,204 control chromosomes in the GnomAD database, including 105,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8320 hom., cov: 34)

Exomes 𝑓: 0.36 ( 96733 hom. )

Consequence

BIN1
NM_139343.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.06

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

myopathy, centronuclear, 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
centronuclear myopathy
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant centronuclear myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive centronuclear myopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 2-127063923-T-C is Benign according to our data. Variant chr2-127063923-T-C is described in ClinVar as Benign. ClinVar VariationId is 158017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139343.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BIN1	NM_139343.3	MANE Select	c.698+10A>G	intron	N/A	NP_647593.1
BIN1	NM_001320642.1		c.617+10A>G	intron	N/A	NP_001307571.1
BIN1	NM_001320641.2		c.605+10A>G	intron	N/A	NP_001307570.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
BIN1	ENST00000316724.10	TSL:1 MANE Select	c.698+10A>G	intron	N/A	ENSP00000316779.5
BIN1	ENST00000357970.7	TSL:1	c.698+10A>G	intron	N/A	ENSP00000350654.3
BIN1	ENST00000346226.7	TSL:1	c.605+10A>G	intron	N/A	ENSP00000315411.3

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47850

AN:

151986

Hom.:

8303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.510

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.349

GnomAD2 exomes

AF:

0.374

AC:

93983

AN:

251006

AF XY:

0.383

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.429

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.358

Gnomad NFE exome

AF:

0.357

Gnomad OTH exome

AF:

0.383

GnomAD4 exome

AF:

0.360

AC:

525349

AN:

1461098

Hom.:

96733

Cov.:

AF XY:

0.364

AC XY:

264810

AN XY:

726902

show subpopulations

African (AFR)

AF:

0.155

AC:

5189

AN:

33476

American (AMR)

AF:

0.424

AC:

18939

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

9094

AN:

26128

East Asian (EAS)

AF:

0.352

AC:

13964

AN:

39692

South Asian (SAS)

AF:

0.492

AC:

42428

AN:

86256

European-Finnish (FIN)

AF:

0.365

AC:

19329

AN:

52900

Middle Eastern (MID)

AF:

0.401

AC:

2314

AN:

5768

European-Non Finnish (NFE)

AF:

0.353

AC:

392441

AN:

1111786

Other (OTH)

AF:

0.359

AC:

21651

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

20679

41359

62038

82718

103397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12626

25252

37878

50504

63130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.315

AC:

47893

AN:

152106

Hom.:

8320

Cov.:

AF XY:

0.322

AC XY:

23960

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.166

AC:

6880

AN:

41486

American (AMR)

AF:

0.409

AC:

6256

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1276

AN:

3470

East Asian (EAS)

AF:

0.392

AC:

2024

AN:

5162

South Asian (SAS)

AF:

0.492

AC:

2378

AN:

4830

European-Finnish (FIN)

AF:

0.353

AC:

3740

AN:

10580

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24032

AN:

67968

Other (OTH)

AF:

0.351

AC:

742

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1722

3444

5165

6887

8609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.316

Hom.:

2456

Bravo

AF:

0.309

Asia WGS

AF:

0.430

AC:

1493

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Myopathy, centronuclear, 2 (3)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.87

(source)

DANN

Benign

0.59

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over