chr16-84294984-G-A

Position:

chr16-84294984-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021197.4(WFDC1):c.13G>A(p.Gly5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00832 in 1,613,164 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 3 hom., cov: 34)

Exomes 𝑓: 0.0087 ( 64 hom. )

Consequence

WFDC1
NM_021197.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.780

Variant links:

Genes affected

WFDC1 (HGNC:15466): (WAP four-disulfide core domain 1) This gene encodes a member of the WAP-type four disulfide core domain family. The WAP-type four-disulfide core domain contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is mapped to chromosome 16q24, an area of frequent loss of heterozygosity in cancers, including prostate, breast and hepatocellular cancers and Wilms' tumor. This gene is downregulated in many cancer types and may be involved in the inhibition of cell proliferation. The encoded protein may also play a role in the susceptibility of certain CD4 memory T cells to human immunodeficiency virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

WFDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027948022).

BP6

Variant 16-84294984-G-A is Benign according to our data. Variant chr16-84294984-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718633.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFDC1	NM_021197.4 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/7	ENST00000219454.10	NP_067020.2	Q9HC57
WFDC1	NM_001282466.2 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/7		NP_001269395.1	Q9HC57
WFDC1	NM_001282467.2 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/7		NP_001269396.1	Q9HC57
WFDC1	XM_047434411.1 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/6		XP_047290367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WFDC1	ENST00000219454.10 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/7	1	NM_021197.4	ENSP00000219454.5	Q9HC57
WFDC1	ENST00000568638.1 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/7	2		ENSP00000456920.1	Q9HC57
WFDC1	ENST00000613603.1 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/1	6		ENSP00000481580.1	A0A087WY77

Frequencies

GnomAD3 genomes

AF:

0.00499

AC:

760

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00848

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00528

AC:

1320

AN:

249968

Hom.:

AF XY:

0.00528

AC XY:

713

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.00343

Gnomad ASJ exome

AF:

0.000500

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000394

Gnomad FIN exome

AF:

0.00242

Gnomad NFE exome

AF:

0.00953

Gnomad OTH exome

AF:

0.00394

GnomAD4 exome

AF:

0.00867

AC:

12660

AN:

1460796

Hom.:

Cov.:

AF XY:

0.00832

AC XY:

6044

AN XY:

726584

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00370

Gnomad4 ASJ exome

AF:

0.000652

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.000465

Gnomad4 FIN exome

AF:

0.00274

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00611

GnomAD4 genome

AF:

0.00499

AC:

760

AN:

152368

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

336

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00216

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00848

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00773

Hom.:

Bravo

AF:

0.00545

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00884

AC:

ExAC

AF:

0.00572

AC:

695

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00834

EpiControl

AF:

0.00937

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.058

DANN

Benign

0.92

DEOGEN2

Benign

0.019

T;T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.41

.;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.55

N;N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

0.63

N;N;.

REVEL

Benign

0.013

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.024

MVP

0.030

MPC

0.020

ClinPred

0.0046

GERP RS

-8.2

Varity_R

0.030

gMVP

0.35

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