11-76198575-A-G

Position:

• chr11-76198575-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
WNT11	NM_004626.3	c.84-1857T>C		intron_variant		ENST00000322563.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT11	ENST00000322563.8	c.84-1857T>C		intron_variant		1	NM_004626.3	P1

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

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.326

Alfa AF: 0.320 Hom.: 12830

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

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: rs4944092; hg19: chr11-75909619;