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

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIF1	NM_007191.5 link	c.827-142dupA		intron_variant	Intron 7 of 9	ENST00000286574.9	NP_009122.2	Q9Y5W5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIF1	ENST00000286574.9 link	c.827-142_827-141insA		intron_variant	Intron 7 of 9	1	NM_007191.5	ENSP00000286574.4		Q9Y5W5
WIF1	ENST00000543094.1 link	c.116-142_116-141insA		intron_variant	Intron 2 of 4	5		ENSP00000439024.1		H0YFK7

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

Gnomad4 AFR exome

AF:

0.202

AC:

1851

AN:

9150

Gnomad4 AMR exome

AF:

0.0579

AC:

544

AN:

9390

Gnomad4 ASJ exome

AF:

0.0532

AC:

461

AN:

8660

Gnomad4 EAS exome

AF:

0.0410

AC:

797

AN:

19422

Gnomad4 SAS exome

AF:

0.0723

AC:

1930

AN:

26680

Gnomad4 FIN exome

AF:

0.0330

AC:

668

AN:

20256

Gnomad4 NFE exome

AF:

0.0388

AC:

9446

AN:

243236

Gnomad4 Remaining exome

AF:

0.0604

AC:

1127

AN:

18664

Heterozygous variant carriers

1349

2698

4047

5396

6745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.225

AC:

0.224936

AN:

0.224936

Gnomad4 AMR

AF:

0.0378

AC:

0.0377737

AN:

0.0377737

Gnomad4 ASJ

AF:

0.0199

AC:

0.0199039

AN:

0.0199039

Gnomad4 EAS

AF:

0.00621

AC:

0.0062144

AN:

0.0062144

Gnomad4 SAS

AF:

0.0615

AC:

0.0615016

AN:

0.0615016

Gnomad4 FIN

AF:

0.00190

AC:

0.00190042

AN:

0.00190042

Gnomad4 NFE

AF:

0.0125

AC:

0.0125427

AN:

0.0125427

Gnomad4 OTH

AF:

0.0746

AC:

0.0746173

AN:

0.0746173

Heterozygous variant carriers

361

722

1083

1444

1805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 19, 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

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over