12-65120486-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007191.5(WIF1):c.219A>G(p.Ala73Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,613,906 control chromosomes in the GnomAD database, including 457,501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44112 hom., cov: 32)

Exomes 𝑓: 0.75 ( 413389 hom. )

Consequence

WIF1
NM_007191.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.09

Publications

27 publications found

Variant links:

Genes affected

WIF1 (HGNC:18081): (WNT inhibitory factor 1) The protein encoded by this gene functions to inhibit WNT proteins, which are extracellular signaling molecules that play a role in embryonic development. This protein contains a WNT inhibitory factor (WIF) domain and five epidermal growth factor (EGF)-like domains, and is thought to be involved in mesoderm segmentation. This gene functions as a tumor suppressor gene, and has been found to be epigenetically silenced in various cancers. [provided by RefSeq, Jun 2010]

WIF1 links:

Genome browser will be placed here

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=-0.81).

BP6

Variant 12-65120486-T-C is Benign according to our data. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-65120486-T-C is described in CliVar as Benign. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIF1	NM_007191.5 link	c.219A>G	p.Ala73Ala	synonymous_variant	Exon 2 of 10	ENST00000286574.9	NP_009122.2	Q9Y5W5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIF1	ENST00000286574.9 link	c.219A>G	p.Ala73Ala	synonymous_variant	Exon 2 of 10	1	NM_007191.5	ENSP00000286574.4		Q9Y5W5
WIF1	ENST00000546001.1 link	c.33A>G	p.Ala11Ala	synonymous_variant	Exon 1 of 4	5		ENSP00000442063.1		F5H8A3

Frequencies

GnomAD3 genomes

AF:

0.760

AC:

115632

AN:

152062

Hom.:

44073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.682

Gnomad AMR

AF:

0.724

Gnomad ASJ

AF:

0.773

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.855

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.782

GnomAD2 exomes

AF:

0.776

AC:

194925

AN:

251322

AF XY:

0.780

show subpopulations

Gnomad AFR exome

AF:

0.769

Gnomad AMR exome

AF:

0.713

Gnomad ASJ exome

AF:

0.787

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.759

Gnomad NFE exome

AF:

0.743

Gnomad OTH exome

AF:

0.775

GnomAD4 exome

AF:

0.750

AC:

1096337

AN:

1461726

Hom.:

413389

Cov.:

AF XY:

0.753

AC XY:

547414

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.768

AC:

25710

AN:

33476

American (AMR)

AF:

0.711

AC:

31764

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.781

AC:

20410

AN:

26130

East Asian (EAS)

AF:

0.999

AC:

39655

AN:

39688

South Asian (SAS)

AF:

0.842

AC:

72572

AN:

86240

European-Finnish (FIN)

AF:

0.753

AC:

40239

AN:

53406

Middle Eastern (MID)

AF:

0.851

AC:

4906

AN:

5768

European-Non Finnish (NFE)

AF:

0.733

AC:

814679

AN:

1111930

Other (OTH)

AF:

0.768

AC:

46402

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

14781

29562

44343

59124

73905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20156

40312

60468

80624

100780

<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:

0.760

AC:

115726

AN:

152180

Hom.:

44112

Cov.:

AF XY:

0.766

AC XY:

56966

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.766

AC:

31813

AN:

41530

American (AMR)

AF:

0.725

AC:

11087

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.773

AC:

2685

AN:

3472

East Asian (EAS)

AF:

0.997

AC:

5171

AN:

5186

South Asian (SAS)

AF:

0.857

AC:

4127

AN:

4818

European-Finnish (FIN)

AF:

0.765

AC:

8098

AN:

10582

Middle Eastern (MID)

AF:

0.827

AC:

243

AN:

294

European-Non Finnish (NFE)

AF:

0.739

AC:

50221

AN:

67968

Other (OTH)

AF:

0.784

AC:

1659

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1430

2859

4289

5718

7148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<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:

0.750

Hom.:

67535

Bravo

AF:

0.756

Asia WGS

AF:

0.920

AC:

3196

AN:

3478

EpiCase

AF:

0.757

EpiControl

AF:

0.771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 05, 2021

GeneDx

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

-0.81

CADD

Benign

3.4

(source)

DANN

Benign

0.49

PhyloP100

-2.1

PromoterAI

0.0035

Neutral

(source)

Mutation Taster

=97/3

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