rs170800

Positions:

• chr20-45708217-T-C

Variant summary

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

The NM_172005.2(WFDC13):​c.*382T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 152,224 control chromosomes in the GnomAD database, including 883 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 0.078 (883 hom., cov: 32)
  • Exomes 𝑓: 0.053 (0 hom.)
• Consequence: WFDC13 NM_172005.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

Genes affected

WFDC13 (HGNC:16131): (WAP four-disulfide core domain 13) This gene encodes a member of the WAP-type four-disulfide core (WFDC) domain family. The WFDC domain, or WAP signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor. Most WFDC gene members are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFDC13	NM_172005.2	c.*382T>C		3_prime_UTR_variant	4/4	ENST00000305479.3	NP_742002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WFDC13	ENST00000305479.3	c.*382T>C		3_prime_UTR_variant	4/4	1	NM_172005.2	ENSP00000302938.2

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11910 AN: 152068 Hom.: 878 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0242

Gnomad OTH AF: 0.0670

GnomAD4 exome AF: 0.0526 AC: 2 AN: 38 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 2 AN XY: 32

Gnomad4 NFE exome AF: 0.0278

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0785 AC: 11944 AN: 152186 Hom.: 883 Cov.: 32 AF XY: 0.0798 AC XY: 5940 AN XY: 74406

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.0154

Gnomad4 FIN AF: 0.0246

Gnomad4 NFE AF: 0.0242

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0617 Hom.: 219

Bravo AF: 0.0916

Asia WGS AF: 0.0610 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.80
DANN	Benign	0.70

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: rs170800; hg19: chr20-44336856;