NM_001256447.2:c.702+12C>T

Variant names:

• chrX-153701995-G-A
• rs1424684303
• NM_001256447.2:c.702+12C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001256447.2(BCAP31):​c.702+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,205,344 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000013 (0 hom. 2 hem.)
• Consequence: BCAP31 NM_001256447.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.579
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-153701995-G-A is Benign according to our data. Variant chrX-153701995-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1933419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL,AR 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.702+12C>T		intron	N/A	NP_001243376.1	P51572-1
	BCAP31	NM_001139457.2		c.903+12C>T		intron	N/A	NP_001132929.1	P51572-2
	BCAP31	NM_001139441.1		c.702+12C>T		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.702+12C>T		intron	N/A	ENSP00000343458.6	P51572-1
	BCAP31	ENST00000458587.8	TSL:1	c.903+12C>T		intron	N/A	ENSP00000392330.2	P51572-2
	BCAP31	ENST00000928875.1		c.783+12C>T		intron	N/A	ENSP00000598934.1

Frequencies

GnomAD3 genomes AF: 0.0000797 AC: 9 AN: 112960 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000161

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: 0.0000750

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000169 AC: 3 AN: 177472 AF XY: 0.00

Gnomad AFR exome AF: 0.000155

Gnomad AMR exome AF: 0.0000374

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000128 AC: 14 AN: 1092384 Hom.: 0 Cov.: 28 AF XY: 0.00000558 AC XY: 2 AN XY: 358368

African (AFR) AF: 0.000114 AC: 3 AN: 26264

American (AMR) AF: 0.0000572 AC: 2 AN: 34982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19272

East Asian (EAS) AF: 0.00 AC: 0 AN: 30110

South Asian (SAS) AF: 0.00 AC: 0 AN: 53674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3920

European-Non Finnish (NFE) AF: 0.0000107 AC: 9 AN: 837850

Other (OTH) AF: 0.00 AC: 0 AN: 45856

GnomAD4 genome AF: 0.0000797 AC: 9 AN: 112960 Hom.: 0 Cov.: 24 AF XY: 0.0000285 AC XY: 1 AN XY: 35110

African (AFR) AF: 0.000161 AC: 5 AN: 31130

American (AMR) AF: 0.00 AC: 0 AN: 10732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3591

South Asian (SAS) AF: 0.00 AC: 0 AN: 2801

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000750 AC: 4 AN: 53327

Other (OTH) AF: 0.00 AC: 0 AN: 1528

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.43
PhyloP100		0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1424684303; hg19: chrX-152967450;