chrX-153715410-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001256447.2(BCAP31):​c.341+132C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 980,718 control chromosomes in the GnomAD database, including 9 homozygotes. There are 236 hemizygotes 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 0.0047 (3 hom., 119 hem., cov: 22)
  • Exomes 𝑓: 0.00057 (6 hom. 117 hem.)
• 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: AR, XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000573 (498/869187) while in subpopulation AFR AF = 0.0183 (388/21239). AF 95% confidence interval is 0.0168. There are 6 homozygotes in GnomAdExome4. There are 117 alleles in the male GnomAdExome4 subpopulation. Median coverage is 14. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256447.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAP31	NM_001256447.2	MANE Select	c.341+132C>G		intron	N/A	NP_001243376.1	P51572-1
	BCAP31	NM_001139457.2		c.542+132C>G		intron	N/A	NP_001132929.1	P51572-2
	BCAP31	NM_001139441.1		c.341+132C>G		intron	N/A	NP_001132913.1	P51572-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAP31	ENST00000345046.12	TSL:1 MANE Select	c.341+132C>G		intron	N/A	ENSP00000343458.6	P51572-1
	BCAP31	ENST00000458587.8	TSL:1	c.542+132C>G		intron	N/A	ENSP00000392330.2	P51572-2
	BCAP31	ENST00000928875.1		c.422+132C>G		intron	N/A	ENSP00000598934.1

Frequencies

GnomAD3 genomes AF: 0.00466 AC: 519 AN: 111478 Hom.: 3 Cov.: 22

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

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: 0.0000941

Gnomad OTH AF: 0.00738

GnomAD4 exome AF: 0.000573 AC: 498 AN: 869187 Hom.: 6 Cov.: 14 AF XY: 0.000481 AC XY: 117 AN XY: 243281

African (AFR) AF: 0.0183 AC: 388 AN: 21239

American (AMR) AF: 0.000941 AC: 27 AN: 28702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14887

East Asian (EAS) AF: 0.00 AC: 0 AN: 28674

South Asian (SAS) AF: 0.00 AC: 0 AN: 42192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36688

Middle Eastern (MID) AF: 0.000436 AC: 1 AN: 2295

European-Non Finnish (NFE) AF: 0.0000442 AC: 29 AN: 656504

Other (OTH) AF: 0.00139 AC: 53 AN: 38006

GnomAD4 genome AF: 0.00465 AC: 519 AN: 111531 Hom.: 3 Cov.: 22 AF XY: 0.00353 AC XY: 119 AN XY: 33735

African (AFR) AF: 0.0155 AC: 474 AN: 30486

American (AMR) AF: 0.00275 AC: 29 AN: 10549

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3543

South Asian (SAS) AF: 0.00 AC: 0 AN: 2652

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000941 AC: 5 AN: 53138

Other (OTH) AF: 0.00729 AC: 11 AN: 1509

Alfa AF: 0.000715 Hom.: 0

Bravo AF: 0.00530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.73
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;