rs133333

Variant names:

• chr22-42016361-G-A
• rs133333
• NM_152613.3:c.63-2950G>A

Variant summary

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

The NM_152613.3(WBP2NL):​c.63-2950G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 151,956 control chromosomes in the GnomAD database, including 40,087 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 0.72 (40087 hom., cov: 30)
• Consequence: WBP2NL NM_152613.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 12 publications found

Genes affected

WBP2NL (HGNC:28389): (WBP2 N-terminal like) WBP2NL is a sperm-specific WW domain-binding protein that promotes meiotic resumption and pronuclear development during oocyte fertilization (Wu et al., 2007 [PubMed 17289678]).[supplied by OMIM, Mar 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 (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WBP2NL	NM_152613.3	c.63-2950G>A		intron_variant	Intron 1 of 5	ENST00000328823.13	NP_689826.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP2NL	ENST00000328823.13	c.63-2950G>A		intron_variant	Intron 1 of 5	1	NM_152613.3	ENSP00000332983.9

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109669 AN: 151836 Hom.: 40073 Cov.: 30

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.722 AC: 109724 AN: 151956 Hom.: 40087 Cov.: 30 AF XY: 0.718 AC XY: 53329 AN XY: 74256

African (AFR) AF: 0.621 AC: 25715 AN: 41428

American (AMR) AF: 0.751 AC: 11466 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2739 AN: 3470

East Asian (EAS) AF: 0.905 AC: 4687 AN: 5180

South Asian (SAS) AF: 0.749 AC: 3601 AN: 4808

European-Finnish (FIN) AF: 0.646 AC: 6803 AN: 10524

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52203 AN: 67968

Other (OTH) AF: 0.732 AC: 1541 AN: 2104

Alfa AF: 0.754 Hom.: 87254

Bravo AF: 0.728

Asia WGS AF: 0.811 AC: 2823 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	0.46
DANN	Benign	0.68
PhyloP100		-0.69
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: rs133333; hg19: chr22-42412365;