rs111450526

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001256447.2(BCAP31):c.383C>T(p.Thr128Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,209,172 control chromosomes in the GnomAD database, including 1 homozygotes. There are 697 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T128T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 50 hem., cov: 24)

Exomes 𝑓: 0.0019 ( 1 hom. 647 hem. )

Consequence

BCAP31
NM_001256447.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 7.61

Publications

3 publications found

Variant links:

Genes affected

BCAP31 (HGNC:16695): (B cell receptor associated protein 31) This gene encodes a member of the B-cell receptor associated protein 31 superfamily. The encoded protein is a multi-pass transmembrane protein of the endoplasmic reticulum that is involved in the anterograde transport of membrane proteins from the endoplasmic reticulum to the Golgi and in caspase 8-mediated apoptosis. Microdeletions in this gene are associated with contiguous ABCD1/DXS1375E deletion syndrome (CADDS), a neonatal disorder. Alternative splicing of this gene results in multiple transcript variants. Two related pseudogenes have been identified on chromosome 16. [provided by RefSeq, Jan 2012]

BCAP31 Gene-Disease associations (from GenCC):

severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome
Inheritance: XL, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet

BCAP31 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022595048).

BP6

Variant X-153704053-G-A is Benign according to our data. Variant chrX-153704053-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 235341.

BS2

High Hemizygotes in GnomAd4 at 50 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
BCAP31	NM_001256447.2 link	c.383C>T	p.Thr128Met	missense_variant	Exon 5 of 8	ENST00000345046.12	NP_001243376.1
BCAP31	NM_001139457.2 link	c.584C>T	p.Thr195Met	missense_variant	Exon 5 of 8		NP_001132929.1
BCAP31	NM_001139441.1 link	c.383C>T	p.Thr128Met	missense_variant	Exon 5 of 8		NP_001132913.1
BCAP31	NM_005745.8 link	c.383C>T	p.Thr128Met	missense_variant	Exon 5 of 8		NP_005736.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAP31	ENST00000345046.12 link	c.383C>T	p.Thr128Met	missense_variant	Exon 5 of 8	1	NM_001256447.2	ENSP00000343458.6

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

154

AN:

112483

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000323

Gnomad AMI

AF:

0.00438

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000490

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00204

Gnomad OTH

AF:

0.00267

GnomAD2 exomes

AF:

0.00138

AC:

253

AN:

183054

AF XY:

0.00136

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000433

Gnomad FIN exome

AF:

0.000255

Gnomad NFE exome

AF:

0.00246

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00187

AC:

2046

AN:

1096636

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

647

AN XY:

362056

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

26372

American (AMR)

AF:

0.00128

AC:

AN:

35182

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19363

East Asian (EAS)

AF:

0.000199

AC:

AN:

30180

South Asian (SAS)

AF:

0.0000370

AC:

AN:

54094

European-Finnish (FIN)

AF:

0.000198

AC:

AN:

40317

Middle Eastern (MID)

AF:

0.000246

AC:

AN:

4061

European-Non Finnish (NFE)

AF:

0.00228

AC:

1918

AN:

841051

Other (OTH)

AF:

0.00126

AC:

AN:

46016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

151

226

302

377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.00137

AC:

154

AN:

112536

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

AN XY:

34704

show subpopulations

African (AFR)

AF:

0.000322

AC:

AN:

31036

American (AMR)

AF:

0.00235

AC:

AN:

10650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2664

East Asian (EAS)

AF:

0.00

AC:

AN:

3583

South Asian (SAS)

AF:

0.00

AC:

AN:

2726

European-Finnish (FIN)

AF:

0.000490

AC:

AN:

6125

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00204

AC:

109

AN:

53331

Other (OTH)

AF:

0.00264

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.00151

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00242

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00135

AC:

164

EpiCase

AF:

0.00213

EpiControl

AF:

0.00267

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Jul 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 01, 2017

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

May 10, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BCAP31-related disorder

Benign:1

Jul 23, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0

.;T;T;.;T;.;T;.;T

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.93

D;.;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.023

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

0.0

.;L;L;.;.;.;.;.;.

PhyloP100

7.6

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.1

N;N;.;.;N;N;N;N;N

REVEL

Uncertain

0.44

Sift

Uncertain

0.011

D;D;.;.;D;D;D;D;D

Sift4G

Benign

0.091

T;D;.;.;.;D;D;.;.

Vest4

0.34

ClinPred

0.042

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.49

Mutation Taster

=90/10

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over