Genetic Variant NM_001256447.2:c.702+13G>A (chrX-153701994-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001256447.2(BCAP31):c.702+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,205,323 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 6 hem., cov: 25)

Exomes 𝑓: 0.000084 ( 0 hom. 31 hem. )

Consequence

BCAP31
NM_001256447.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.434

Publications

0 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: AR, XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

BCAP31 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant X-153701994-C-T is Benign according to our data. Variant chrX-153701994-C-T is described in ClinVar as Benign. ClinVar VariationId is 1899325.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCAP31	NM_001256447.2	MANE Select	c.702+13G>A	intron	N/A	NP_001243376.1	P51572-1
BCAP31	NM_001139457.2		c.903+13G>A	intron	N/A	NP_001132929.1	P51572-2
BCAP31	NM_001139441.1		c.702+13G>A	intron	N/A	NP_001132913.1	P51572-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BCAP31	ENST00000345046.12	TSL:1 MANE Select	c.702+13G>A	intron	N/A	ENSP00000343458.6	P51572-1
BCAP31	ENST00000458587.8	TSL:1	c.903+13G>A	intron	N/A	ENSP00000392330.2	P51572-2
BCAP31	ENST00000928875.1		c.783+13G>A	intron	N/A	ENSP00000598934.1

Frequencies

GnomAD3 genomes

AF:

0.000398

AC:

AN:

112997

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000279

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:

0.0000937

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000102

AC:

AN:

177056

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.0000749

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000380

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000842

AC:

AN:

1092326

Hom.:

Cov.:

AF XY:

0.0000865

AC XY:

AN XY:

358362

show subpopulations

African (AFR)

AF:

0.000724

AC:

AN:

26254

American (AMR)

AF:

0.000114

AC:

AN:

34949

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19235

East Asian (EAS)

AF:

0.00

AC:

AN:

30119

South Asian (SAS)

AF:

0.00

AC:

AN:

53598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40456

Middle Eastern (MID)

AF:

0.000256

AC:

AN:

3909

European-Non Finnish (NFE)

AF:

0.0000764

AC:

AN:

837955

Other (OTH)

AF:

0.0000872

AC:

AN:

45851

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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

<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:

0.000398

AC:

AN:

112997

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

AN XY:

35127

show subpopulations

African (AFR)

AF:

0.00119

AC:

AN:

31127

American (AMR)

AF:

0.000279

AC:

AN:

10738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3591

South Asian (SAS)

AF:

0.00

AC:

AN:

2801

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6269

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000937

AC:

AN:

53360

Other (OTH)

AF:

0.00

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000214

Hom.:

Bravo

AF:

0.000442

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.64

(source)

DANN

Benign

0.43

PhyloP100

-0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over