chr20-45579372-C-T

Variant names:

• chr20-45579372-C-T
• rs7273669
• NM_130896.3:c.-125G>A

Variant summary

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

The NM_130896.3(WFDC8):​c.-125G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,275,030 control chromosomes in the GnomAD database, including 96,391 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 0.33 (9352 hom., cov: 31)
  • Exomes 𝑓: 0.38 (87039 hom.)
• Consequence: WFDC8 NM_130896.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

Genes affected

WFDC8 (HGNC:16163): (WAP four-disulfide core domain 8) 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. The encoded protein contains a Kunitz-inhibitor domain, in addition to three WFDC domains. Most WFDC genes are localized to chromosome 20q12-q13 in two clusters: centromeric and telomeric. This gene belongs to the telomeric cluster. Two alternatively spliced transcript variants have been found for this gene, and they encode the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WFDC8	NM_130896.3	c.-125G>A		upstream_gene_variant		ENST00000289953.3	NP_570966.2
WFDC8	NM_181510.3	c.-125G>A		upstream_gene_variant			NP_852611.2
WFDC8	XM_017028119.2	c.-125G>A		upstream_gene_variant			XP_016883608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WFDC8	ENST00000289953.3	c.-125G>A		upstream_gene_variant		1	NM_130896.3	ENSP00000289953.2
WFDC8	ENST00000357199.8	c.-125G>A		upstream_gene_variant		1		ENSP00000361735.3

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50809 AN: 151810 Hom.: 9350 Cov.: 31

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.00387

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.380 AC: 426372 AN: 1123102 Hom.: 87039 Cov.: 14 AF XY: 0.378 AC XY: 215099 AN XY: 569574

Gnomad4 AFR exome AF: 0.242

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.000722

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.334 AC: 50811 AN: 151928 Hom.: 9352 Cov.: 31 AF XY: 0.330 AC XY: 24460 AN XY: 74216

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.00369

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.323

Alfa AF: 0.383 Hom.: 1436

Bravo AF: 0.317

Asia WGS AF: 0.111 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7273669; hg19: chr20-44208011; COSMIC: COSV51489582;