Genetic Variant WIF1:c.827-142dupA (chr12-65056267-C-CT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_007191.5(WIF1):c.827-142dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 475,434 control chromosomes in the GnomAD database, including 750 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.078 ( 728 hom., cov: 31)

Exomes 𝑓: 0.047 ( 22 hom. )

Consequence

WIF1
NM_007191.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 12-65056267-C-CT is Benign according to our data. Variant chr12-65056267-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1181766.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007191.5. 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
	WIF1	NM_007191.5	MANE Select	c.827-142dupA		intron	N/A	NP_009122.2	Q9Y5W5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WIF1	ENST00000286574.9	TSL:1 MANE Select	c.827-142_827-141insA	intron	N/A	ENSP00000286574.4	Q9Y5W5
WIF1	ENST00000954483.1		c.797-142_797-141insA	intron	N/A	ENSP00000624542.1
WIF1	ENST00000954485.1		c.827-172_827-171insA	intron	N/A	ENSP00000624544.1

Frequencies

GnomAD3 genomes

AF:

0.0776

AC:

9148

AN:

117960

Hom.:

725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.0278

Gnomad AMR

AF:

0.0378

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.00646

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.00190

Gnomad MID

AF:

0.0658

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.0748

GnomAD4 exome

AF:

0.0474

AC:

16953

AN:

357464

Hom.:

AF XY:

0.0483

AC XY:

8939

AN XY:

185130

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.202

AC:

1851

AN:

9150

American (AMR)

AF:

0.0579

AC:

544

AN:

9390

Ashkenazi Jewish (ASJ)

AF:

0.0532

AC:

461

AN:

8660

East Asian (EAS)

AF:

0.0410

AC:

797

AN:

19422

South Asian (SAS)

AF:

0.0723

AC:

1930

AN:

26680

European-Finnish (FIN)

AF:

0.0330

AC:

668

AN:

20256

Middle Eastern (MID)

AF:

0.0643

AC:

129

AN:

2006

European-Non Finnish (NFE)

AF:

0.0388

AC:

9446

AN:

243236

Other (OTH)

AF:

0.0604

AC:

1127

AN:

18664

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.331

Heterozygous variant carriers

1349

2698

4047

5396

6745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

166

332

498

664

830

<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:

0.0776

AC:

9151

AN:

117970

Hom.:

728

Cov.:

AF XY:

0.0780

AC XY:

4378

AN XY:

56154

show subpopulations

African (AFR)

AF:

0.225

AC:

7579

AN:

33694

American (AMR)

AF:

0.0378

AC:

414

AN:

10960

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

2914

East Asian (EAS)

AF:

0.00621

AC:

AN:

3862

South Asian (SAS)

AF:

0.0615

AC:

231

AN:

3756

European-Finnish (FIN)

AF:

0.00190

AC:

AN:

5262

Middle Eastern (MID)

AF:

0.0493

AC:

AN:

142

European-Non Finnish (NFE)

AF:

0.0125

AC:

691

AN:

55092

Other (OTH)

AF:

0.0746

AC:

117

AN:

1568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

361

722

1083

1444

1805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.00104

Hom.:

Bravo

AF:

0.0683

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

12-65056267-CTTTT-CTTTTT

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