13-41065289-TAAAAAAAAAAAAAA-TAAAAAAAAAA

Variant names:

• chr13-41065289-TAAAA-T
• rs58699334
• NM_007187.5:c.262+20_262+23delAAAA

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP6 BS1

The ENST00000379487.5(WBP4):​c.262+3_262+6delAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,248,114 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000049 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0080 (0 hom.)
• Consequence: WBP4 ENST00000379487.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 13-41065289-TAAAA-T is Benign according to our data. Variant chr13-41065289-TAAAA-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00796 (9281/1166326) while in subpopulation AMR AF= 0.0293 (457/15604). AF 95% confidence interval is 0.0271. There are 0 homozygotes in gnomad4_exome. There are 4985 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WBP4	NM_007187.5	c.262+20_262+23delAAAA		intron_variant	Intron 4 of 9	ENST00000379487.5	NP_009118.1
WBP4	XM_005266245.3	c.355+20_355+23delAAAA		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+3_262+6delAAAA		splice_region_variant, intron_variant	Intron 4 of 9	1	NM_007187.5	ENSP00000368801.3

Frequencies

GnomAD3 genomes AF: 0.0000489 AC: 4 AN: 81788 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

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: 0.0000976

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0375 AC: 1281 AN: 34198 Hom.: 0 AF XY: 0.0384 AC XY: 701 AN XY: 18256

Gnomad AFR exome AF: 0.0420

Gnomad AMR exome AF: 0.0407

Gnomad ASJ exome AF: 0.0278

Gnomad EAS exome AF: 0.0380

Gnomad SAS exome AF: 0.0371

Gnomad FIN exome AF: 0.0383

Gnomad NFE exome AF: 0.0369

Gnomad OTH exome AF: 0.0273

GnomAD4 exome AF: 0.00796 AC: 9281 AN: 1166326 Hom.: 0 AF XY: 0.00877 AC XY: 4985 AN XY: 568302

Gnomad4 AFR exome AF: 0.0124

Gnomad4 AMR exome AF: 0.0293

Gnomad4 ASJ exome AF: 0.0169

Gnomad4 EAS exome AF: 0.0214

Gnomad4 SAS exome AF: 0.0169

Gnomad4 FIN exome AF: 0.0220

Gnomad4 NFE exome AF: 0.00589

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome AF: 0.0000489 AC: 4 AN: 81788 Hom.: 0 Cov.: 25 AF XY: 0.0000262 AC XY: 1 AN XY: 38220

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000976

Gnomad4 OTH AF: 0.00

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;