Genetic Variant WBP4:c.262+20_262+23delAAAA (chr13-41065289-TAAAA-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP6BS1

The ENST00000379487.5(WBP4):c.262+3_262+6delAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,248,114 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000049 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0080 ( 0 hom. )

Consequence

WBP4
ENST00000379487.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.966

Variant links:

Genes affected

WBP4 (HGNC:12739): (WW domain binding protein 4) This gene encodes WW domain-containing binding protein 4. The WW domain represents a small and compact globular structure that interacts with proline-rich ligands. This encoded protein is a general spliceosomal protein that may play a role in cross-intron bridging of U1 and U2 snRNPs in the spliceosomal complex A. [provided by RefSeq, Jul 2008]

WBP4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 13-41065289-TAAAA-T is Benign according to our data. Variant chr13-41065289-TAAAA-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00796 (9281/1166326) while in subpopulation AMR AF= 0.0293 (457/15604). AF 95% confidence interval is 0.0271. There are 0 homozygotes in gnomad4_exome. There are 4985 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WBP4	NM_007187.5 link	c.262+20_262+23delAAAA		intron_variant	Intron 4 of 9	ENST00000379487.5	NP_009118.1	O75554-1
WBP4	XM_005266245.3 link	c.355+20_355+23delAAAA		intron_variant	Intron 4 of 9		XP_005266302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP4	ENST00000379487.5 link	c.262+3_262+6delAAAA		splice_region_variant, intron_variant	Intron 4 of 9	1	NM_007187.5	ENSP00000368801.3		O75554-1

Frequencies

GnomAD3 genomes

AF:

0.0000489

AC:

AN:

81788

Hom.:

Cov.:

show subpopulations

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:

0.0000976

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0375

AC:

1281

AN:

34198

Hom.:

AF XY:

0.0384

AC XY:

701

AN XY:

18256

show subpopulations

Gnomad AFR exome

AF:

0.0420

Gnomad AMR exome

AF:

0.0407

Gnomad ASJ exome

AF:

0.0278

Gnomad EAS exome

AF:

0.0380

Gnomad SAS exome

AF:

0.0371

Gnomad FIN exome

AF:

0.0383

Gnomad NFE exome

AF:

0.0369

Gnomad OTH exome

AF:

0.0273

GnomAD4 exome

AF:

0.00796

AC:

9281

AN:

1166326

Hom.:

AF XY:

0.00877

AC XY:

4985

AN XY:

568302

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.0293

Gnomad4 ASJ exome

AF:

0.0169

Gnomad4 EAS exome

AF:

0.0214

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.0220

Gnomad4 NFE exome

AF:

0.00589

Gnomad4 OTH exome

AF:

0.0113

GnomAD4 genome

AF:

0.0000489

AC:

AN:

81788

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

38220

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000976

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

13-41065289-TAAAAAAAAAAAAAA-TAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over