rs10504824

Variant names:

• chr8-86406035-G-A
• rs10504824
• NM_007013.4:c.724+3832G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007013.4(WWP1):​c.724+3832G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 152,188 control chromosomes in the GnomAD database, including 316 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.054 (316 hom., cov: 32)
• Consequence: WWP1 NM_007013.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 3 publications found

Genes affected

WWP1 (HGNC:17004): (WW domain containing E3 ubiquitin protein ligase 1) WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 4 tandem WW domains and a HECT (homologous to the E6-associated protein carboxyl terminus) domain. The encoded protein belongs to a family of NEDD4-like proteins, which are E3 ubiquitin-ligase molecules and regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Alternative splicing of this gene generates at least 6 transcript variants; however, the full length nature of these transcripts has not been defined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWP1	NM_007013.4	c.724+3832G>A		intron_variant	Intron 8 of 24	ENST00000517970.6	NP_008944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWP1	ENST00000517970.6	c.724+3832G>A		intron_variant	Intron 8 of 24	1	NM_007013.4	ENSP00000427793.1
WWP1	ENST00000265428.4	c.724+3832G>A		intron_variant	Intron 6 of 22	1		ENSP00000265428.4
WWP1	ENST00000518683.5	n.379-5503G>A		intron_variant	Intron 4 of 14	1
WWP1	ENST00000520374.5	n.66+915G>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 8261 AN: 152070 Hom.: 317 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0565

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0863

Gnomad OTH AF: 0.0575

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0543 AC: 8260 AN: 152188 Hom.: 316 Cov.: 32 AF XY: 0.0510 AC XY: 3798 AN XY: 74408

African (AFR) AF: 0.0142 AC: 589 AN: 41540

American (AMR) AF: 0.0456 AC: 696 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0916 AC: 318 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0112 AC: 54 AN: 4818

European-Finnish (FIN) AF: 0.0565 AC: 598 AN: 10588

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0863 AC: 5866 AN: 67992

Other (OTH) AF: 0.0559 AC: 118 AN: 2110

Alfa AF: 0.0771 Hom.: 831

Bravo AF: 0.0529

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.45
DANN	Benign	0.61
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs10504824; hg19: chr8-87418264;