rs3785054

Positions:

• chr16-84327871-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFDC1	NM_021197.4	c.*15+916A>G		intron_variant		ENST00000219454.10	NP_067020.2
WFDC1	NM_001282466.2	c.*15+916A>G		intron_variant			NP_001269395.1
WFDC1	NM_001282467.2	c.*15+916A>G		intron_variant			NP_001269396.1
WFDC1	XM_047434411.1	c.*15+916A>G		intron_variant			XP_047290367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WFDC1	ENST00000219454.10	c.*15+916A>G		intron_variant		1	NM_021197.4	ENSP00000219454.5
WFDC1	ENST00000568638.1	c.*15+916A>G		intron_variant		2		ENSP00000456920.1
WFDC1	ENST00000622779.1	n.2208A>G		non_coding_transcript_exon_variant	1/1	6
WFDC1	ENST00000567056.1	n.3631+916A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42167 AN: 151840 Hom.: 5924 Cov.: 32

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: 35 AN: 90 Hom.: 4 Cov.: 0 AF XY: 0.388 AC XY: 31 AN XY: 80

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.278 AC: 42210 AN: 151958 Hom.: 5935 Cov.: 32 AF XY: 0.282 AC XY: 20967 AN XY: 74266

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.253

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
DANN	Benign	0.30

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

Other links and lift over

dbSNP: rs3785054; hg19: chr16-84361477;