dbSNP rs3748705: WLS:p.Ala144Ala (chr1-68159195-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_024911.7(WLS):c.432G>A(p.Ala144Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,613,290 control chromosomes in the GnomAD database, including 99,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 8895 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90392 hom. )

Consequence

WLS
NM_024911.7 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0650

Publications

28 publications found

Variant links:

Genes affected

WLS (HGNC:30238): (Wnt ligand secretion mediator) Enables Wnt-protein binding activity and identical protein binding activity. Involved in positive regulation of cell communication and protein transport. Located in several cellular components, including Golgi apparatus; early endosome; and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

WLS links:

GNG12-AS1 (HGNC:43938): (GNG12, DIRAS3 and WLS antisense RNA 1)

GNG12-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.018).

BP6

Variant 1-68159195-C-T is Benign according to our data. Variant chr1-68159195-C-T is described in ClinVar as Benign. ClinVar VariationId is 2585666.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.065 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WLS	NM_024911.7 link	c.432G>A	p.Ala144Ala	synonymous_variant	Exon 3 of 12	ENST00000262348.9	NP_079187.3	Q5T9L3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WLS	ENST00000262348.9 link	c.432G>A	p.Ala144Ala	synonymous_variant	Exon 3 of 12	1	NM_024911.7	ENSP00000262348.4		Q5T9L3-1

Frequencies

GnomAD3 genomes

AF:

0.334

AC:

50657

AN:

151832

Hom.:

8894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.343

GnomAD2 exomes

AF:

0.367

AC:

92178

AN:

251192

AF XY:

0.367

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.286

Gnomad EAS exome

AF:

0.456

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.349

AC:

510128

AN:

1461338

Hom.:

90392

Cov.:

AF XY:

0.349

AC XY:

253482

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.245

AC:

8199

AN:

33460

American (AMR)

AF:

0.400

AC:

17870

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

7532

AN:

26110

East Asian (EAS)

AF:

0.433

AC:

17185

AN:

39676

South Asian (SAS)

AF:

0.353

AC:

30416

AN:

86164

European-Finnish (FIN)

AF:

0.458

AC:

24467

AN:

53394

Middle Eastern (MID)

AF:

0.364

AC:

2100

AN:

5764

European-Non Finnish (NFE)

AF:

0.343

AC:

381251

AN:

1111734

Other (OTH)

AF:

0.350

AC:

21108

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

16936

33872

50808

67744

84680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12220

24440

36660

48880

61100

<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:

0.334

AC:

50680

AN:

151952

Hom.:

8895

Cov.:

AF XY:

0.339

AC XY:

25174

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.246

AC:

10206

AN:

41460

American (AMR)

AF:

0.383

AC:

5842

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

974

AN:

3468

East Asian (EAS)

AF:

0.436

AC:

2245

AN:

5148

South Asian (SAS)

AF:

0.365

AC:

1760

AN:

4818

European-Finnish (FIN)

AF:

0.458

AC:

4824

AN:

10544

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23609

AN:

67944

Other (OTH)

AF:

0.342

AC:

721

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1671

3343

5014

6686

8357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.341

Hom.:

15311

Bravo

AF:

0.326

Asia WGS

AF:

0.373

AC:

1296

AN:

3478

EpiCase

AF:

0.351

EpiControl

AF:

0.346

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Zaki syndrome

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.0

(source)

DANN

Benign

0.75

PhyloP100

0.065

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over