X-153715410-G-A

Variant names:

• chrX-153715410-G-A
• rs17091297
• NM_001256447.2:c.341+132C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001256447.2(BCAP31):​c.341+132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 111,480 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
• Consequence: BCAP31 NM_001256447.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• Publications: 1 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAP31	NM_001256447.2	c.341+132C>T		intron_variant	Intron 4 of 7	ENST00000345046.12	NP_001243376.1
BCAP31	NM_001139457.2	c.542+132C>T		intron_variant	Intron 4 of 7		NP_001132929.1
BCAP31	NM_001139441.1	c.341+132C>T		intron_variant	Intron 4 of 7		NP_001132913.1
BCAP31	NM_005745.8	c.341+132C>T		intron_variant	Intron 4 of 7		NP_005736.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAP31	ENST00000345046.12	c.341+132C>T		intron_variant	Intron 4 of 7	1	NM_001256447.2	ENSP00000343458.6

Frequencies

GnomAD3 genomes AF: 0.00000897 AC: 1 AN: 111480 Hom.: 0 Cov.: 22

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 14

GnomAD4 genome AF: 0.00000897 AC: 1 AN: 111480 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33672

African (AFR) AF: 0.00 AC: 0 AN: 30420

American (AMR) AF: 0.00 AC: 0 AN: 10536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3554

South Asian (SAS) AF: 0.00 AC: 0 AN: 2660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6107

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53145

Other (OTH) AF: 0.00 AC: 0 AN: 1490

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.78
PhyloP100		0.46

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

Other links and lift over

dbSNP: rs17091297; hg19: chrX-152980865;