Genetic Variant BCAP31:c.341+132C>G (chrX-153715410-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.455

Publications

1 publications found

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 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

BCAP31 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
BCAP31	NM_001256447.2 link	c.341+132C>G	intron_variant	Intron 4 of 7	ENST00000345046.12	NP_001243376.1	P51572-1
BCAP31	NM_001139457.2 link	c.542+132C>G	intron_variant	Intron 4 of 7		NP_001132929.1	P51572-2
BCAP31	NM_001139441.1 link	c.341+132C>G	intron_variant	Intron 4 of 7		NP_001132913.1	P51572-1
BCAP31	NM_005745.8 link	c.341+132C>G	intron_variant	Intron 4 of 7		NP_005736.3	P51572-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAP31	ENST00000345046.12 link	c.341+132C>G		intron_variant	Intron 4 of 7	1	NM_001256447.2	ENSP00000343458.6		P51572-1

Frequencies

GnomAD3 genomes

AF:

0.00466

AC:

519

AN:

111478

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.000481

AC XY:

117

AN XY:

243281

show subpopulations

African (AFR)

AF:

0.0183

AC:

388

AN:

21239

American (AMR)

AF:

0.000941

AC:

AN:

28702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14887

East Asian (EAS)

AF:

0.00

AC:

AN:

28674

South Asian (SAS)

AF:

0.00

AC:

AN:

42192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36688

Middle Eastern (MID)

AF:

0.000436

AC:

AN:

2295

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

656504

Other (OTH)

AF:

0.00139

AC:

AN:

38006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00465

AC:

519

AN:

111531

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

119

AN XY:

33735

show subpopulations

African (AFR)

AF:

0.0155

AC:

474

AN:

30486

American (AMR)

AF:

0.00275

AC:

AN:

10549

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3543

South Asian (SAS)

AF:

0.00

AC:

AN:

2652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6107

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000941

AC:

AN:

53138

Other (OTH)

AF:

0.00729

AC:

AN:

1509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000715

Hom.:

Bravo

AF:

0.00530

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.3

(source)

DANN

Benign

0.73

PhyloP100

0.46

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over