Genetic Variant WIF1:c.827-142delA (chr12-65056267-CT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007191.5(WIF1):c.827-142delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 448,948 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., cov: 31)

Exomes 𝑓: 0.11 ( 0 hom. )

Consequence

WIF1
NM_007191.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Variant has high frequency in the EAS (0.139) population. However there is too low homozygotes in high coverage region: (expected more than 743, got 0).

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.827-142delA		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.827-142delA	intron	N/A	ENSP00000286574.4	Q9Y5W5
WIF1	ENST00000954483.1		c.797-142delA	intron	N/A	ENSP00000624542.1
WIF1	ENST00000954485.1		c.827-172delA	intron	N/A	ENSP00000624544.1

Frequencies

GnomAD3 genomes

AF:

0.000993

AC:

117

AN:

117860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00128

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00181

Gnomad SAS

AF:

0.000530

Gnomad FIN

AF:

0.00420

Gnomad MID

AF:

0.00658

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.00128

GnomAD4 exome

AF:

0.110

AC:

36435

AN:

331078

Hom.:

AF XY:

0.112

AC XY:

19202

AN XY:

171116

show subpopulations

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

African (AFR)

AF:

0.0805

AC:

700

AN:

8698

American (AMR)

AF:

0.143

AC:

1235

AN:

8634

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

1028

AN:

7776

East Asian (EAS)

AF:

0.143

AC:

2501

AN:

17438

South Asian (SAS)

AF:

0.119

AC:

2980

AN:

25064

European-Finnish (FIN)

AF:

0.118

AC:

2196

AN:

18540

Middle Eastern (MID)

AF:

0.0839

AC:

157

AN:

1872

European-Non Finnish (NFE)

AF:

0.104

AC:

23581

AN:

225866

Other (OTH)

AF:

0.120

AC:

2057

AN:

17190

⚠️ 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: 0.267

Heterozygous variant carriers

3853

7706

11558

15411

19264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

284

568

852

1136

1420

<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:

0.000993

AC:

117

AN:

117870

Hom.:

Cov.:

AF XY:

0.000963

AC XY:

AN XY:

56072

show subpopulations

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

African (AFR)

AF:

0.00107

AC:

AN:

33722

American (AMR)

AF:

0.00128

AC:

AN:

10950

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2908

East Asian (EAS)

AF:

0.00182

AC:

AN:

3856

South Asian (SAS)

AF:

0.000266

AC:

AN:

3754

European-Finnish (FIN)

AF:

0.00420

AC:

AN:

5240

Middle Eastern (MID)

AF:

0.00704

AC:

AN:

142

European-Non Finnish (NFE)

AF:

0.000618

AC:

AN:

55012

Other (OTH)

AF:

0.00128

AC:

AN:

1566

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.384

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000289

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=100/0

polymorphism

(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.

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