13-41065289-TAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAA

Variant names:

• chr13-41065289-T-TAAA
• rs58699334
• NM_007187.5:c.262+21_262+23dupAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000379487.5(WBP4):​c.262+2_262+3insAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 1,198,040 control chromosomes in the GnomAD database, including 1,262 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (1247 hom., cov: 25)
  • Exomes 𝑓: 0.037 (15 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.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WBP4	NM_007187.5	c.262+21_262+23dupAAA		intron_variant	Intron 4 of 9	ENST00000379487.5	NP_009118.1
WBP4	XM_005266245.3	c.355+21_355+23dupAAA		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+3insAAA		splice_region_variant, intron_variant	Intron 4 of 9	1	NM_007187.5	ENSP00000368801.3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 16398 AN: 81294 Hom.: 1247 Cov.: 25

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.0104 AC: 357 AN: 34198 Hom.: 8 AF XY: 0.0106 AC XY: 193 AN XY: 18256

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.00814

Gnomad ASJ exome AF: 0.0116

Gnomad EAS exome AF: 0.00686

Gnomad SAS exome AF: 0.00938

Gnomad FIN exome AF: 0.00282

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0372 AC: 41521 AN: 1116718 Hom.: 15 Cov.: 0 AF XY: 0.0360 AC XY: 19682 AN XY: 546048

Gnomad4 AFR exome AF: 0.0193

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.0117

Gnomad4 EAS exome AF: 0.00868

Gnomad4 SAS exome AF: 0.0171

Gnomad4 FIN exome AF: 0.0215

Gnomad4 NFE exome AF: 0.0415

Gnomad4 OTH exome AF: 0.0311

GnomAD4 genome AF: 0.202 AC: 16397 AN: 81322 Hom.: 1247 Cov.: 25 AF XY: 0.194 AC XY: 7367 AN XY: 37978

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0976

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;