Variant 12-65051408-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007191.5(WIF1):c.1081C>A(p.Pro361Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00166 in 1,613,846 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 7 hom. )

Consequence

WIF1
NM_007191.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.40

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:

ENSG00000198671 (HGNC:):

ENSG00000198671 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009321958).

BP6

Variant 12-65051408-G-T is Benign according to our data. Variant chr12-65051408-G-T is described in ClinVar as [Benign]. Clinvar id is 710452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00905 (1379/152348) while in subpopulation AFR AF= 0.0306 (1272/41568). AF 95% confidence interval is 0.0292. There are 14 homozygotes in gnomad4. There are 656 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIF1	NM_007191.5 link	c.1081C>A	p.Pro361Thr	missense_variant	10/10	ENST00000286574.9	NP_009122.2	Q9Y5W5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WIF1	ENST00000286574.9 link	c.1081C>A	p.Pro361Thr	missense_variant	10/10	1	NM_007191.5	ENSP00000286574.4	Q9Y5W5
WIF1	ENST00000543094.1 link	c.328C>A	p.Pro110Thr	missense_variant	5/5	5		ENSP00000439024.1	H0YFK7
ENSG00000198671	ENST00000360528.3 link	n.1036-2694G>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00899

AC:

1369

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0304

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00246

AC:

616

AN:

249982

Hom.:

AF XY:

0.00177

AC XY:

239

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.0330

Gnomad AMR exome

AF:

0.00183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000892

AC:

1304

AN:

1461498

Hom.:

Cov.:

AF XY:

0.000740

AC XY:

538

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.0301

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.00905

AC:

1379

AN:

152348

Hom.:

Cov.:

AF XY:

0.00881

AC XY:

656

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0306

Gnomad4 AMR

AF:

0.00555

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00161

Hom.:

Bravo

AF:

0.0101

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0347

AC:

153

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00298

AC:

362

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000594

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	Labcorp Genetics (formerly Invitae), Labcorp	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0093

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0010

B;.

Vest4

0.33

MVP

0.81

MPC

0.36

ClinPred

0.11

GERP RS

3.6

Varity_R

0.27

gMVP

0.50

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