NM_001256447.2:c.719C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001256447.2(BCAP31):c.719C>T(p.Pro240Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,205,503 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 52 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00017 ( 0 hom. 50 hem. )

Consequence

BCAP31
NM_001256447.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.27

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07551587).

BP6

Variant X-153700959-G-A is Benign according to our data. Variant chrX-153700959-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2414267.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAP31	NM_001256447.2 link	c.719C>T	p.Pro240Leu	missense_variant	Exon 8 of 8	ENST00000345046.12	NP_001243376.1	P51572-1
BCAP31	NM_001139457.2 link	c.920C>T	p.Pro307Leu	missense_variant	Exon 8 of 8		NP_001132929.1	P51572-2
BCAP31	NM_001139441.1 link	c.719C>T	p.Pro240Leu	missense_variant	Exon 8 of 8		NP_001132913.1	P51572-1
BCAP31	NM_005745.8 link	c.719C>T	p.Pro240Leu	missense_variant	Exon 8 of 8		NP_005736.3	P51572-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAP31	ENST00000345046.12 link	c.719C>T	p.Pro240Leu	missense_variant	Exon 8 of 8	1	NM_001256447.2	ENSP00000343458.6		P51572-1

Frequencies

GnomAD3 genomes

AF:

0.0000808

AC:

AN:

111378

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

33572

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000946

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000400

AC:

AN:

174818

Hom.:

AF XY:

0.0000330

AC XY:

AN XY:

60566

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000166

AC:

182

AN:

1094125

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

360249

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.0000653

GnomAD4 genome

AF:

0.0000808

AC:

AN:

111378

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

33572

show subpopulations

Gnomad4 AFR

AF:

0.0000327

Gnomad4 AMR

AF:

0.0000946

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Dec 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 240 of the BCAP31 protein (p.Pro240Leu). This variant is present in population databases (rs200212822, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with BCAP31-related conditions. ClinVar contains an entry for this variant (Variation ID: 2414267). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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. -

Inborn genetic diseases

Benign:1

Apr 24, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

.;T;T;.

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.82

T;.;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.076

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;M;M;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.7

N;N;.;.

REVEL

Benign

0.023

Sift

Uncertain

0.029

D;T;.;.

Sift4G

Benign

0.12

T;T;.;.

Polyphen

0.030

.;B;B;.

Vest4

0.17

MVP

0.40

MPC

1.1

ClinPred

0.13

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.066

gMVP

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over