Genetic Variant WNT11:p.Ser271Ser (chr11-76191641-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004626.3(WNT11):c.813G>A(p.Ser271Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,614,040 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S271S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0080 ( 18 hom., cov: 33)

Exomes 𝑓: 0.00086 ( 18 hom. )

Consequence

WNT11
NM_004626.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.44

Publications

1 publications found

Variant links:

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]

WNT11 links:

ENSG00000254933 (HGNC:):

ENSG00000254933 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-76191641-C-T is Benign according to our data. Variant chr11-76191641-C-T is described in ClinVar as Benign. ClinVar VariationId is 783635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.44 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.008 (1218/152342) while in subpopulation AFR AF = 0.0281 (1167/41578). AF 95% confidence interval is 0.0267. There are 18 homozygotes in GnomAd4. There are 588 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1218 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004626.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT11	NM_004626.3	MANE Select	c.813G>A	p.Ser271Ser	synonymous	Exon 4 of 5	NP_004617.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT11	ENST00000322563.8	TSL:1 MANE Select	c.813G>A	p.Ser271Ser	synonymous	Exon 4 of 5	ENSP00000325526.3	O96014
WNT11	ENST00000961018.1		c.843G>A	p.Ser281Ser	synonymous	Exon 5 of 6	ENSP00000631077.1
WNT11	ENST00000961028.1		c.843G>A	p.Ser281Ser	synonymous	Exon 5 of 6	ENSP00000631087.1

Frequencies

GnomAD3 genomes

AF:

0.00799

AC:

1216

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00222

AC:

558

AN:

251314

AF XY:

0.00171

show subpopulations

Gnomad AFR exome

AF:

0.0302

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000928

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000863

AC:

1261

AN:

1461698

Hom.:

Cov.:

AF XY:

0.000763

AC XY:

555

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.0294

AC:

984

AN:

33480

American (AMR)

AF:

0.000984

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000958

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000459

AC:

AN:

1112006

Other (OTH)

AF:

0.00192

AC:

116

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

165

247

330

412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00800

AC:

1218

AN:

152342

Hom.:

Cov.:

AF XY:

0.00789

AC XY:

588

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0281

AC:

1167

AN:

41578

American (AMR)

AF:

0.00170

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68036

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000232

Hom.:

Bravo

AF:

0.00910

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.97

(source)

DANN

Benign

0.83

PhyloP100

-2.4

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over