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GeneBe

2-127048561-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_139343.3(BIN1):c.1747G>A(p.Val583Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152224 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

BIN1
NM_139343.3 missense

Scores

5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

Links

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.32408577).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIN1NM_139343.3 linkuse as main transcriptc.1747G>A p.Val583Ile missense_variant 19/19 ENST00000316724.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIN1ENST00000316724.10 linkuse as main transcriptc.1747G>A p.Val583Ile missense_variant 19/191 NM_139343.3 O00499-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152224
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
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
GnomAD3 exomes
AF:
0.0000441
AC:
11
AN:
249508
Hom.:
0
AF XY:
0.0000592
AC XY:
8
AN XY:
135042
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461600
Hom.:
0
AF XY:
0.0000220
AC XY:
16
AN XY:
727116
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000928
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Myopathy, centronuclear, 2 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeNov 26, 2021This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 583 of the BIN1 protein (p.Val583Ile). This variant is present in population databases (rs759691190, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with BIN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 579601). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.31
Cadd
Benign
23
Dann
Uncertain
1.0
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.96
D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.062
D
MetaRNN
Benign
0.32
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.85
T
MutationTaster
Benign
0.74
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.31
N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.16
Sift
Benign
0.16
T;T;T;T;T;T;T;T;T;D;T
Sift4G
Benign
0.11
T;T;T;T;T;T;T;T;T;T;T
Polyphen
1.0
D;P;P;D;D;B;D;D;D;B;D
Vest4
0.49
MutPred
0.43
.;.;.;.;.;.;.;.;.;Gain of catalytic residue at P585 (P = 0.0301);.;
MVP
0.71
MPC
0.54
ClinPred
0.26
T
GERP RS
4.9
Varity_R
0.55
gMVP
0.37

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.

Other links and lift over

dbSNP: rs759691190; hg19: chr2-127806137; COSMIC: COSV52115768; COSMIC: COSV52115768; API