Variant 12-65067677-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007191.5(WIF1):c.634+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,608,848 control chromosomes in the GnomAD database, including 1,898 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 869 hom., cov: 32)

Exomes 𝑓: 0.017 ( 1029 hom. )

Consequence

WIF1
NM_007191.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.262

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-65067677-A-G is Benign according to our data. Variant chr12-65067677-A-G is described in ClinVar as [Benign]. Clinvar id is 1228551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIF1	NM_007191.5 linkuse as main transcript	c.634+18T>C		intron_variant		ENST00000286574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIF1	ENST00000286574.9 linkuse as main transcript	c.634+18T>C		intron_variant		1	NM_007191.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0647

AC:

9838

AN:

152152

Hom.:

861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0281

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0495

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00970

Gnomad OTH

AF:

0.0578

GnomAD3 exomes

AF:

0.0273

AC:

6817

AN:

250076

Hom.:

407

AF XY:

0.0256

AC XY:

3465

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.0134

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.0509

Gnomad FIN exome

AF:

0.000695

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.0170

AC:

24756

AN:

1456578

Hom.:

1029

Cov.:

AF XY:

0.0176

AC XY:

12781

AN XY:

724850

show subpopulations

Gnomad4 AFR exome

AF:

0.208

Gnomad4 AMR exome

AF:

0.0155

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.000530

Gnomad4 SAS exome

AF:

0.0513

Gnomad4 FIN exome

AF:

0.00133

Gnomad4 NFE exome

AF:

0.00951

Gnomad4 OTH exome

AF:

0.0250

GnomAD4 genome

AF:

0.0648

AC:

9863

AN:

152270

Hom.:

869

Cov.:

AF XY:

0.0633

AC XY:

4714

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.0280

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0491

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00970

Gnomad4 OTH

AF:

0.0572

Alfa

AF:

0.0387

Hom.:

Bravo

AF:

0.0705

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.010

DANN

Benign

0.27

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