rs775494528

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_139343.3(BIN1):c.1046C>T(p.Pro349Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000777 in 1,543,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P349P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

BIN1
NM_139343.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.57

Publications

5 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):

centronuclear myopathy
Inheritance: AD, AR, SD Classification: DEFINITIVE, LIMITED Submitted by: ClinGen
myopathy, centronuclear, 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
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: Uncertain_significance. The variant received 0 ACMG points.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
BIN1	NM_139343.3	MANE Select	c.1046C>T	p.Pro349Leu	missense	Exon 12 of 19	NP_647593.1	O00499-1
BIN1	NM_001320642.1		c.965C>T	p.Pro322Leu	missense	Exon 12 of 19	NP_001307571.1	O00499
BIN1	NM_001320641.2		c.953C>T	p.Pro318Leu	missense	Exon 11 of 18	NP_001307570.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BIN1	ENST00000316724.10	TSL:1 MANE Select	c.1046C>T	p.Pro349Leu	missense	Exon 12 of 19	ENSP00000316779.5	O00499-1
BIN1	ENST00000346226.7	TSL:1	c.953C>T	p.Pro318Leu	missense	Exon 11 of 16	ENSP00000315411.3	O00499-2
BIN1	ENST00000259238.8	TSL:1	c.998C>T	p.Pro333Leu	missense	Exon 12 of 16	ENSP00000259238.4	O00499-11

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000651

AC:

AN:

153516

AF XY:

0.0000124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000234

GnomAD4 exome

AF:

0.00000719

AC:

AN:

1391392

Hom.:

Cov.:

AF XY:

0.00000584

AC XY:

AN XY:

685018

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31506

American (AMR)

AF:

0.00

AC:

AN:

35314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25040

East Asian (EAS)

AF:

0.00

AC:

AN:

35484

South Asian (SAS)

AF:

0.0000127

AC:

AN:

78486

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5398

European-Non Finnish (NFE)

AF:

0.00000745

AC:

AN:

1073360

Other (OTH)

AF:

0.00

AC:

AN:

57620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000132

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41398

American (AMR)

AF:

0.0000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Myopathy, centronuclear, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.73

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.9

PhyloP100

7.6

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-7.5

REVEL

Uncertain

0.38

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.042

Polyphen

1.0

Vest4

0.48

MVP

0.72

MPC

0.89

ClinPred

1.0

GERP RS

4.5

Varity_R

0.67

gMVP

0.65

Mutation Taster

=60/40

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over