13-41065289-TAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000379487.5(WBP4):​c.262+2_262+3insA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,243,866 control chromosomes in the GnomAD database, including 59 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (23 hom., cov: 25)
  • Exomes 𝑓: 0.020 (36 hom.)
• Consequence: WBP4 ENST00000379487.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0148 (1212/81698) while in subpopulation AFR AF= 0.0353 (748/21198). AF 95% confidence interval is 0.0332. There are 23 homozygotes in gnomad4. There are 576 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WBP4	NM_007187.5	c.262+23dupA		intron_variant	Intron 4 of 9	ENST00000379487.5	NP_009118.1
WBP4	XM_005266245.3	c.355+23dupA		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	c.262+2_262+3insA		splice_region_variant, intron_variant	Intron 4 of 9	1	NM_007187.5	ENSP00000368801.3

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 1211 AN: 81670 Hom.: 23 Cov.: 25

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.0171

Gnomad AMR AF: 0.0250

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00283

Gnomad SAS AF: 0.00534

Gnomad FIN AF: 0.00277

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00559

Gnomad OTH AF: 0.0138

GnomAD3 exomes AF: 0.0189 AC: 645 AN: 34198 Hom.: 15 AF XY: 0.0173 AC XY: 316 AN XY: 18256

Gnomad AFR exome AF: 0.0233

Gnomad AMR exome AF: 0.0230

Gnomad ASJ exome AF: 0.0147

Gnomad EAS exome AF: 0.0211

Gnomad SAS exome AF: 0.0161

Gnomad FIN exome AF: 0.00789

Gnomad NFE exome AF: 0.0185

Gnomad OTH exome AF: 0.0210

GnomAD4 exome AF: 0.0201 AC: 23382 AN: 1162168 Hom.: 36 Cov.: 0 AF XY: 0.0203 AC XY: 11512 AN XY: 567016

Gnomad4 AFR exome AF: 0.0194

Gnomad4 AMR exome AF: 0.0220

Gnomad4 ASJ exome AF: 0.0149

Gnomad4 EAS exome AF: 0.0130

Gnomad4 SAS exome AF: 0.0208

Gnomad4 FIN exome AF: 0.0254

Gnomad4 NFE exome AF: 0.0202

Gnomad4 OTH exome AF: 0.0208

GnomAD4 genome AF: 0.0148 AC: 1212 AN: 81698 Hom.: 23 Cov.: 25 AF XY: 0.0151 AC XY: 576 AN XY: 38206

Gnomad4 AFR AF: 0.0353

Gnomad4 AMR AF: 0.0252

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00284

Gnomad4 SAS AF: 0.00535

Gnomad4 FIN AF: 0.00277

Gnomad4 NFE AF: 0.00559

Gnomad4 OTH AF: 0.0128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs58699334; hg19: chr13-41639425;