rs111450526

Variant summary

Our verdict is Benign. Variant got -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).

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

2
5
10

Clinical Significance

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

Conservation

PhyloP100: 7.61
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 235341.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2, Likely_benign=1}. Variant chrX-153704053-G-A is described in Lovd as [Likely_benign].
BS2
High Hemizygotes in GnomAd4 at 50 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BCAP31NM_001256447.2 linkc.383C>T p.Thr128Met missense_variant Exon 5 of 8 ENST00000345046.12 NP_001243376.1 P51572-1
BCAP31NM_001139457.2 linkc.584C>T p.Thr195Met missense_variant Exon 5 of 8 NP_001132929.1 P51572-2
BCAP31NM_001139441.1 linkc.383C>T p.Thr128Met missense_variant Exon 5 of 8 NP_001132913.1 P51572-1
BCAP31NM_005745.8 linkc.383C>T p.Thr128Met missense_variant Exon 5 of 8 NP_005736.3 P51572-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BCAP31ENST00000345046.12 linkc.383C>T p.Thr128Met missense_variant Exon 5 of 8 1 NM_001256447.2 ENSP00000343458.6 P51572-1

Frequencies

GnomAD3 genomes
AF:
0.00137
AC:
154
AN:
112483
Hom.:
0
Cov.:
24
AF XY:
0.00144
AC XY:
50
AN XY:
34641
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
GnomAD3 exomes
AF:
0.00138
AC:
253
AN:
183054
Hom.:
0
AF XY:
0.00136
AC XY:
92
AN XY:
67502
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 SAS exome
AF:
0.00
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.:
1
Cov.:
30
AF XY:
0.00179
AC XY:
647
AN XY:
362056
show subpopulations
Gnomad4 AFR exome
AF:
0.000265
Gnomad4 AMR exome
AF:
0.00128
Gnomad4 ASJ exome
AF:
0.0000516
Gnomad4 EAS exome
AF:
0.000199
Gnomad4 SAS exome
AF:
0.0000370
Gnomad4 FIN exome
AF:
0.000198
Gnomad4 NFE exome
AF:
0.00228
Gnomad4 OTH exome
AF:
0.00126
GnomAD4 genome
AF:
0.00137
AC:
154
AN:
112536
Hom.:
0
Cov.:
24
AF XY:
0.00144
AC XY:
50
AN XY:
34704
show subpopulations
Gnomad4 AFR
AF:
0.000322
Gnomad4 AMR
AF:
0.00235
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000490
Gnomad4 NFE
AF:
0.00204
Gnomad4 OTH
AF:
0.00264
Alfa
AF:
0.00204
Hom.:
29
Bravo
AF:
0.00151
TwinsUK
AF:
0.00108
AC:
4
ALSPAC
AF:
0.00242
AC:
7
ESP6500AA
AF:
0.000261
AC:
1
ESP6500EA
AF:
0.00163
AC:
11
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
Likely benign, no assertion criteria providedclinical testingLaboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)-- -
Benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsMay 10, 2016- -
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2017- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 14, 2021- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 20, 2025- -
BCAP31-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 23, 2020This 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
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.19
.;T;T;.;T;.;T;.;T
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.93
D;.;D;D;D;D;D;D;D
M_CAP
Pathogenic
0.41
D
MetaRNN
Benign
0.023
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
1.9
.;L;L;.;.;.;.;.;.
PrimateAI
Uncertain
0.62
T
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;.;.
Polyphen
0.99
.;D;D;.;.;.;.;.;.
Vest4
0.34
MVP
0.64
MPC
1.8
ClinPred
0.042
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs111450526; hg19: chrX-152969508; API