13-41065289-TAAAAAAAAAAAAAA-TAAAAAAAAAAAAA

Variant names:

• chr13-41065289-TA-T
• rs58699334
• NM_007187.5:c.262+23delA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The ENST00000379487.5(WBP4):​c.262+3delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,233,398 control chromosomes in the GnomAD database, including 10 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0046 (2 hom., cov: 25)
  • Exomes 𝑓: 0.23 (8 hom.)
• Consequence: WBP4 ENST00000379487.5 splice_region, intron
• Clinical Significance: Benign/Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.0850
• Publications: 1 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 13-41065289-TA-T is Benign according to our data. Variant chr13-41065289-TA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1285194.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 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+23delA		intron	N/A	NP_009118.1	O75554-1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.00459 AC: 375 AN: 81782 Hom.: 2 Cov.: 25

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00509

Gnomad ASJ AF: 0.000479

Gnomad EAS AF: 0.00177

Gnomad SAS AF: 0.00190

Gnomad FIN AF: 0.00461

Gnomad MID AF: 0.00893

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.00460

GnomAD2 exomes AF: 0.137 AC: 4698 AN: 34198 AF XY: 0.135

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.163

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.161

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.226 AC: 260322 AN: 1151588 Hom.: 8 Cov.: 0 AF XY: 0.224 AC XY: 125896 AN XY: 561996

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

African (AFR) AF: 0.230 AC: 5696 AN: 24772

American (AMR) AF: 0.172 AC: 2744 AN: 15928

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 3583 AN: 16680

East Asian (EAS) AF: 0.199 AC: 5918 AN: 29792

South Asian (SAS) AF: 0.191 AC: 9966 AN: 52076

European-Finnish (FIN) AF: 0.184 AC: 4569 AN: 24892

Middle Eastern (MID) AF: 0.237 AC: 786 AN: 3316

European-Non Finnish (NFE) AF: 0.231 AC: 216539 AN: 937360

Other (OTH) AF: 0.225 AC: 10521 AN: 46772

⚠️ 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.

GnomAD4 genome AF: 0.00461 AC: 377 AN: 81810 Hom.: 2 Cov.: 25 AF XY: 0.00484 AC XY: 185 AN XY: 38250

African (AFR) AF: 0.0117 AC: 248 AN: 21234

American (AMR) AF: 0.00523 AC: 37 AN: 7076

Ashkenazi Jewish (ASJ) AF: 0.000479 AC: 1 AN: 2088

East Asian (EAS) AF: 0.00178 AC: 5 AN: 2816

South Asian (SAS) AF: 0.00191 AC: 5 AN: 2622

European-Finnish (FIN) AF: 0.00461 AC: 15 AN: 3252

Middle Eastern (MID) AF: 0.00943 AC: 1 AN: 106

European-Non Finnish (NFE) AF: 0.00144 AC: 59 AN: 40992

Other (OTH) AF: 0.00549 AC: 6 AN: 1092

Alfa AF: 0.00 Hom.: 98

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs58699334; hg19: chr13-41639425; COSMIC: COSV65273929; COSMIC: COSV65273929;