dbSNP rs3762371: WLS:c.666+20C>T (chr1-68155079-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024911.7(WLS):c.666+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,609,386 control chromosomes in the GnomAD database, including 128,561 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 0.34 ( 9445 hom., cov: 32)

Exomes 𝑓: 0.40 ( 119116 hom. )

Consequence

WLS
NM_024911.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.876

Publications

17 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WLS	NM_024911.7 link	c.666+20C>T		intron_variant	Intron 4 of 11	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.666+20C>T		intron_variant	Intron 4 of 11	1	NM_024911.7	ENSP00000262348.4		Q5T9L3-1

Frequencies

GnomAD3 genomes

AF:

0.337

AC:

51150

AN:

151896

Hom.:

9444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.372

GnomAD2 exomes

AF:

0.364

AC:

90171

AN:

247780

AF XY:

0.366

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.432

Gnomad ASJ exome

AF:

0.442

Gnomad EAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.398

AC:

579982

AN:

1457374

Hom.:

119116

Cov.:

AF XY:

0.397

AC XY:

287845

AN XY:

724726

show subpopulations

African (AFR)

AF:

0.186

AC:

6220

AN:

33402

American (AMR)

AF:

0.426

AC:

18905

AN:

44406

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

11401

AN:

25868

East Asian (EAS)

AF:

0.150

AC:

5939

AN:

39600

South Asian (SAS)

AF:

0.325

AC:

27800

AN:

85506

European-Finnish (FIN)

AF:

0.311

AC:

16500

AN:

52990

Middle Eastern (MID)

AF:

0.357

AC:

2053

AN:

5754

European-Non Finnish (NFE)

AF:

0.422

AC:

468410

AN:

1109636

Other (OTH)

AF:

0.378

AC:

22754

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

16842

33683

50525

67366

84208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14176

28352

42528

56704

70880

<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:

0.337

AC:

51170

AN:

152012

Hom.:

9445

Cov.:

AF XY:

0.332

AC XY:

24699

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.201

AC:

8344

AN:

41486

American (AMR)

AF:

0.396

AC:

6052

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

1540

AN:

3462

East Asian (EAS)

AF:

0.160

AC:

825

AN:

5162

South Asian (SAS)

AF:

0.308

AC:

1484

AN:

4818

European-Finnish (FIN)

AF:

0.307

AC:

3243

AN:

10564

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.419

AC:

28446

AN:

67942

Other (OTH)

AF:

0.375

AC:

790

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1655

3310

4964

6619

8274

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:

0.402

Hom.:

22369

Bravo

AF:

0.338

Asia WGS

AF:

0.226

AC:

785

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

(source)

DANN

Benign

0.46

PhyloP100

-0.88

Mutation Taster

=99/1

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

Computational scores

Splicing

Publications

Other links and lift over