dbSNP rs3785054: WFDC1:c.*15+916A>G (chr16-84327871-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021197.4(WFDC1):c.*15+916A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,048 control chromosomes in the GnomAD database, including 5,939 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 5935 hom., cov: 32)

Exomes 𝑓: 0.39 ( 4 hom. )

Consequence

WFDC1
NM_021197.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.935

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
WFDC1	NM_021197.4 link	c.*15+916A>G	intron_variant	Intron 6 of 6	ENST00000219454.10	NP_067020.2
WFDC1	NM_001282466.2 link	c.*15+916A>G	intron_variant	Intron 6 of 6		NP_001269395.1
WFDC1	NM_001282467.2 link	c.*15+916A>G	intron_variant	Intron 6 of 6		NP_001269396.1
WFDC1	XM_047434411.1 link	c.*15+916A>G	intron_variant	Intron 5 of 5		XP_047290367.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
WFDC1	ENST00000219454.10 link	c.*15+916A>G	intron_variant	Intron 6 of 6	1	NM_021197.4	ENSP00000219454.5
WFDC1	ENST00000622779.1 link	n.2208A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
WFDC1	ENST00000568638.1 link	c.*15+916A>G	intron_variant	Intron 6 of 6	2		ENSP00000456920.1
WFDC1	ENST00000567056.1 link	n.3631+916A>G	intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42167

AN:

151840

Hom.:

5924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.359

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.255

GnomAD4 exome

AF:

0.389

AC:

AN:

Hom.:

Cov.:

AF XY:

0.388

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.397

AC:

AN:

Other (OTH)

AF:

0.400

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.278

AC:

42210

AN:

151958

Hom.:

5935

Cov.:

AF XY:

0.282

AC XY:

20967

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.298

AC:

12361

AN:

41450

American (AMR)

AF:

0.250

AC:

3819

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

515

AN:

3470

East Asian (EAS)

AF:

0.360

AC:

1853

AN:

5152

South Asian (SAS)

AF:

0.293

AC:

1410

AN:

4812

European-Finnish (FIN)

AF:

0.346

AC:

3651

AN:

10548

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17775

AN:

67938

Other (OTH)

AF:

0.253

AC:

534

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1599

3198

4797

6396

7995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.273

Hom.:

706

Bravo

AF:

0.272

Asia WGS

AF:

0.340

AC:

1181

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.25

(source)

DANN

Benign

0.30

PhyloP100

-0.94

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over