Genetic Variant WBP4:c.262+13_262+23dupAAAAAAAAAAA (chr13-41065289-T-TAAAAAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000379487.5(WBP4):c.262+2_262+3insAAAAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000633 in 1,263,998 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000086 ( 1 hom., cov: 25)

Exomes 𝑓: 8.5e-7 ( 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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+13_262+23dupAAAAAAAAAAA		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+3insAAAAAAAAAAA	splice_region intron	N/A	ENSP00000368801.3	O75554-1
WBP4	ENST00000953016.1		c.262+2_262+3insAAAAAAAAAAA	splice_region intron	N/A	ENSP00000623075.1
WBP4	ENST00000953017.1		c.199+2_199+3insAAAAAAAAAAA	splice_region intron	N/A	ENSP00000623076.1

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

81788

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000142

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:

0.000308

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000732

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.46e-7

AC:

AN:

1182182

Hom.:

Cov.:

AF XY:

0.00000173

AC XY:

AN XY:

576660

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

25344

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

53154

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3382

European-Non Finnish (NFE)

AF:

0.00000104

AC:

AN:

963992

Other (OTH)

AF:

0.00

AC:

AN:

47860

⚠️ 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: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000856

AC:

AN:

81816

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

38254

show subpopulations

African (AFR)

AF:

0.000141

AC:

AN:

21234

American (AMR)

AF:

0.00

AC:

AN:

7076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2088

East Asian (EAS)

AF:

0.00

AC:

AN:

2816

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:

0.0000732

AC:

AN:

41000

Other (OTH)

AF:

0.00

AC:

AN:

1092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

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:

0.00282

Hom.:

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

Publications

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13-41065289-TAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over