rs1270070847

Variant names:

• chrX-153702033-A-C
• rs1270070847
• NM_001256447.2:c.676T>G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001256447.2(BCAP31):​c.676T>G​(p.Leu226Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,210,446 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0000073 (0 hom. 3 hem.)
• Consequence: BCAP31 NM_001256447.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.91

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.42313).
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAP31	NM_001256447.2	c.676T>G	p.Leu226Val	missense_variant	Exon 7 of 8	ENST00000345046.12	NP_001243376.1
BCAP31	NM_001139457.2	c.877T>G	p.Leu293Val	missense_variant	Exon 7 of 8		NP_001132929.1
BCAP31	NM_001139441.1	c.676T>G	p.Leu226Val	missense_variant	Exon 7 of 8		NP_001132913.1
BCAP31	NM_005745.8	c.676T>G	p.Leu226Val	missense_variant	Exon 7 of 8		NP_005736.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAP31	ENST00000345046.12	c.676T>G	p.Leu226Val	missense_variant	Exon 7 of 8	1	NM_001256447.2	ENSP00000343458.6

Frequencies

GnomAD3 genomes AF: 0.00000884 AC: 1 AN: 113082 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 35222

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000187

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000729 AC: 8 AN: 1097364 Hom.: 0 Cov.: 29 AF XY: 0.00000827 AC XY: 3 AN XY: 362886

Gnomad4 AFR exome AF: 0.00

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: 0.00000950

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000884 AC: 1 AN: 113082 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 35222

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000187

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:2

Oct 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 226 of the BCAP31 protein (p.Leu226Val). This variant is not present in population databases (gnomAD no frequency). 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: 1932475). 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 disruptive. 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. -

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BCAP31: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;T;T;.
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Pathogenic	0.98	D;.;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.42	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	.;M;M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D;D;.;.
REVEL	Uncertain	0.29
Sift	Benign	0.13	T;D;.;.
Sift4G	Uncertain	0.051	T;D;.;.
Polyphen		1.0	.;D;D;.
Vest4		0.68
MutPred		0.32		.;Gain of MoRF binding (P = 0.1034);Gain of MoRF binding (P = 0.1034);.;
MVP		0.88
MPC		1.8
ClinPred		0.99	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.90
gMVP		0.61

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

Other links and lift over

dbSNP: rs1270070847; hg19: chrX-152967488;