rs4944092

Variant names:

• chr11-76198575-A-G
• rs4944092
• NM_004626.3:c.84-1857T>C

Variant summary

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

The NM_004626.3(WNT11):​c.84-1857T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,082 control chromosomes in the GnomAD database, including 9,483 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 0.35 (9483 hom., cov: 33)
• Consequence: WNT11 NM_004626.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681
• Publications: 30 publications found

Genes affected

WNT11 (HGNC:12776): (Wnt family member 11) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 97%, 85%, and 63% amino acid identity with mouse, chicken, and Xenopus Wnt11 protein, respectively. This gene may play roles in the development of skeleton, kidney and lung, and is considered to be a plausible candidate gene for High Bone Mass Syndrome. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT11	NM_004626.3	c.84-1857T>C		intron_variant	Intron 1 of 4	ENST00000322563.8	NP_004617.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT11	ENST00000322563.8	c.84-1857T>C		intron_variant	Intron 1 of 4	1	NM_004626.3	ENSP00000325526.3

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52816 AN: 151964 Hom.: 9483 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.347 AC: 52843 AN: 152082 Hom.: 9483 Cov.: 33 AF XY: 0.344 AC XY: 25569 AN XY: 74342

African (AFR) AF: 0.428 AC: 17766 AN: 41476

American (AMR) AF: 0.356 AC: 5452 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1079 AN: 5176

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4812

European-Finnish (FIN) AF: 0.323 AC: 3412 AN: 10572

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22266 AN: 67970

Other (OTH) AF: 0.326 AC: 688 AN: 2108

Alfa AF: 0.328 Hom.: 29915

Bravo AF: 0.352

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.2
DANN	Benign	0.86
PhyloP100		0.68
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: rs4944092; hg19: chr11-75909619;