Genetic Variant WBP4:c.262+20_262+23dupAAAA (chr13-41065289-T-TAAAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000379487.5(WBP4):c.262+2_262+3insAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,260,258 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 25)

Exomes 𝑓: 0.0015 ( 2 hom. )

Consequence

WBP4
ENST00000379487.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities
Inheritance: AR Classification: MODERATE Submitted by: G2P

WBP4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379487.5. 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
	WBP4	NM_007187.5	MANE Select	c.262+20_262+23dupAAAA		intron	N/A	NP_009118.1	O75554-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WBP4	ENST00000379487.5	TSL:1 MANE Select	c.262+2_262+3insAAAA	splice_region intron	N/A	ENSP00000368801.3	O75554-1
WBP4	ENST00000953016.1		c.262+2_262+3insAAAA	splice_region intron	N/A	ENSP00000623075.1
WBP4	ENST00000953017.1		c.199+2_199+3insAAAA	splice_region intron	N/A	ENSP00000623076.1

Frequencies

GnomAD3 genomes

AF:

0.00242

AC:

198

AN:

81718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00543

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

Gnomad ASJ

AF:

0.000479

Gnomad EAS

AF:

0.00283

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000308

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.00368

GnomAD4 exome

AF:

0.00146

AC:

1718

AN:

1178512

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

870

AN XY:

575008

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00150

AC:

AN:

25264

American (AMR)

AF:

0.00143

AC:

AN:

16128

Ashkenazi Jewish (ASJ)

AF:

0.00100

AC:

AN:

16946

East Asian (EAS)

AF:

0.000697

AC:

AN:

30122

South Asian (SAS)

AF:

0.00273

AC:

145

AN:

53106

European-Finnish (FIN)

AF:

0.00266

AC:

AN:

25148

Middle Eastern (MID)

AF:

0.000592

AC:

AN:

3376

European-Non Finnish (NFE)

AF:

0.00139

AC:

1335

AN:

960718

Other (OTH)

AF:

0.00147

AC:

AN:

47704

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.353

Heterozygous variant carriers

119

237

356

474

593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.00242

AC:

198

AN:

81746

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

AN XY:

38216

show subpopulations

African (AFR)

AF:

0.00542

AC:

115

AN:

21214

American (AMR)

AF:

0.00184

AC:

AN:

7072

Ashkenazi Jewish (ASJ)

AF:

0.000479

AC:

AN:

2086

East Asian (EAS)

AF:

0.00284

AC:

AN:

2814

South Asian (SAS)

AF:

0.00

AC:

AN:

2622

European-Finnish (FIN)

AF:

0.000308

AC:

AN:

3250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

106

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

40958

Other (OTH)

AF:

0.00366

AC:

AN:

1092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00125

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.085

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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13-41065289-TAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAA

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