rs1533767

Positions:

• chr11-76194756-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004626.3(WNT11):​c.408C>T​(p.Pro136Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,553,706 control chromosomes in the GnomAD database, including 53,486 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 0.23 (4347 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49139 hom.)
• Consequence: WNT11 NM_004626.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746

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]

ENSG00000254933 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.746 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT11	NM_004626.3	c.408C>T	p.Pro136Pro	synonymous_variant	3/5	ENST00000322563.8	NP_004617.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT11	ENST00000322563.8	c.408C>T	p.Pro136Pro	synonymous_variant	3/5	1	NM_004626.3	ENSP00000325526.3
ENSG00000254933	ENST00000527314.1	n.298G>A		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34735 AN: 151940 Hom.: 4339 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.251

GnomAD3 exomes AF: 0.268 AC: 42756 AN: 159648 Hom.: 5949 AF XY: 0.268 AC XY: 22810 AN XY: 84992

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.339

Gnomad ASJ exome AF: 0.302

Gnomad EAS exome AF: 0.204

Gnomad SAS exome AF: 0.272

Gnomad FIN exome AF: 0.300

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.265

GnomAD4 exome AF: 0.263 AC: 368931 AN: 1401648 Hom.: 49139 Cov.: 58 AF XY: 0.264 AC XY: 182471 AN XY: 691900

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.262

GnomAD4 genome AF: 0.229 AC: 34769 AN: 152058 Hom.: 4347 Cov.: 32 AF XY: 0.230 AC XY: 17129 AN XY: 74330

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.252

Alfa AF: 0.250 Hom.: 1616

Bravo AF: 0.229

Asia WGS AF: 0.266 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.89

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: rs1533767; hg19: chr11-75905800; COSMIC: COSV59443540;