dbSNP rs1026024: WIF1:p.Cys310Cys (chr12-65055206-G-A) – ACMG Classification: Benign (-21 pts)

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.930C>T(p.Cys310Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,390 control chromosomes in the GnomAD database, including 990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 115 hom., cov: 33)

Exomes 𝑓: 0.011 ( 875 hom. )

Consequence

WIF1
NM_007191.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.432

Publications

5 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=-0.6).

BP6

Variant 12-65055206-G-A is Benign according to our data. Variant chr12-65055206-G-A is described in ClinVar as Benign. ClinVar VariationId is 1236341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.432 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIF1	NM_007191.5 link	c.930C>T	p.Cys310Cys	synonymous_variant	Exon 9 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.930C>T	p.Cys310Cys	synonymous_variant	Exon 9 of 10	1	NM_007191.5	ENSP00000286574.4		Q9Y5W5
WIF1	ENST00000543094.1 link	c.177C>T	p.Cys59Cys	synonymous_variant	Exon 4 of 5	5		ENSP00000439024.1		H0YFK7

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1876

AN:

152138

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0274

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.0743

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.0303

AC:

7592

AN:

250564

AF XY:

0.0289

show subpopulations

Gnomad AFR exome

AF:

0.00246

Gnomad AMR exome

AF:

0.0627

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000538

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0105

AC:

15357

AN:

1461134

Hom.:

875

Cov.:

AF XY:

0.0116

AC XY:

8429

AN XY:

726818

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

33448

American (AMR)

AF:

0.0578

AC:

2576

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.00168

AC:

AN:

26114

East Asian (EAS)

AF:

0.148

AC:

5870

AN:

39678

South Asian (SAS)

AF:

0.0602

AC:

5178

AN:

86010

European-Finnish (FIN)

AF:

0.000225

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000316

AC:

351

AN:

1111766

Other (OTH)

AF:

0.0209

AC:

1260

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

663

1325

1988

2650

3313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<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:

0.0123

AC:

1869

AN:

152256

Hom.:

115

Cov.:

AF XY:

0.0146

AC XY:

1086

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00284

AC:

118

AN:

41542

American (AMR)

AF:

0.0272

AC:

416

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.175

AC:

910

AN:

5186

South Asian (SAS)

AF:

0.0742

AC:

358

AN:

4826

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68022

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

178

266

355

444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00620

Hom.:

Bravo

AF:

0.0148

Asia WGS

AF:

0.125

AC:

434

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000474

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

-0.60

CADD

Benign

5.8

(source)

DANN

Benign

0.56

PhyloP100

-0.43

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