rs16963349

Positions:

• chr16-84304628-T-C
• chr16-84304628-T-G

Variant summary

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

The NM_021197.4(WFDC1):​c.145-8333T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 152,250 control chromosomes in the GnomAD database, including 1,197 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 0.071 (1197 hom., cov: 33)
• Consequence: WFDC1 NM_021197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WFDC1	NM_021197.4	c.145-8333T>C		intron_variant		ENST00000219454.10
WFDC1	NM_001282466.2	c.145-8333T>C		intron_variant
WFDC1	NM_001282467.2	c.145-8333T>C		intron_variant
WFDC1	XM_047434411.1	c.145-8333T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WFDC1	ENST00000219454.10	c.145-8333T>C		intron_variant		1	NM_021197.4	P1
WFDC1	ENST00000568638.1	c.145-8333T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0706 AC: 10739 AN: 152132 Hom.: 1194 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.0540

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0708 AC: 10779 AN: 152250 Hom.: 1197 Cov.: 33 AF XY: 0.0699 AC XY: 5203 AN XY: 74448

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.0127

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0308 Hom.: 125

Bravo AF: 0.0783

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.058
DANN	Benign	0.66

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: rs16963349; hg19: chr16-84338234;