Genetic Variant WBP4:c.262+17_262+23dupAAAAAAA (chr13-41065289-T-TAAAAAAA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000379487.5(WBP4):c.262+2_262+3insAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,263,960 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000049 ( 1 hom., cov: 25)

Exomes 𝑓: 0.000019 ( 0 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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new If you want to explore the variant's impact on the transcript ENST00000379487.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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+17_262+23dupAAAAAAA		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+3insAAAAAAA	splice_region intron	N/A	ENSP00000368801.3	O75554-1
WBP4	ENST00000953016.1		c.262+2_262+3insAAAAAAA	splice_region intron	N/A	ENSP00000623075.1
WBP4	ENST00000953017.1		c.199+2_199+3insAAAAAAA	splice_region intron	N/A	ENSP00000623076.1

Frequencies

GnomAD3 genomes

AF:

0.0000489

AC:

AN:

81788

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000472

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:

0.0000732

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000195

AC:

AN:

1182172

Hom.:

Cov.:

AF XY:

0.0000191

AC XY:

AN XY:

576654

show subpopulations

African (AFR)

AF:

0.0000395

AC:

AN:

25344

American (AMR)

AF:

0.000186

AC:

AN:

16146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16968

East Asian (EAS)

AF:

0.00

AC:

AN:

30142

South Asian (SAS)

AF:

0.0000564

AC:

AN:

53152

European-Finnish (FIN)

AF:

0.0000397

AC:

AN:

25194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3382

European-Non Finnish (NFE)

AF:

0.0000145

AC:

AN:

963984

Other (OTH)

AF:

0.0000209

AC:

AN:

47860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000489

AC:

AN:

81788

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

38222

show subpopulations

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

African (AFR)

AF:

0.0000472

AC:

AN:

21186

American (AMR)

AF:

0.00

AC:

AN:

7072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2088

East Asian (EAS)

AF:

0.00

AC:

AN:

2828

South Asian (SAS)

AF:

0.00

AC:

AN:

2628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

112

European-Non Finnish (NFE)

AF:

0.0000732

AC:

AN:

41002

Other (OTH)

AF:

0.00

AC:

AN:

1088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.085

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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