rs6094192

Positions:

• chr20-45669157-G-A

Variant summary

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

The NM_147197.2(WFDC11):​c.-134+1021C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 151,918 control chromosomes in the GnomAD database, including 2,520 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 0.18 (2520 hom., cov: 32)
• Consequence: WFDC11 NM_147197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

Genes affected

WFDC11 (HGNC:20478): (WAP four-disulfide core domain 11) 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFDC11	NM_147197.2	c.-134+1021C>T		intron_variant		ENST00000324384.4	NP_671730.1
WFDC11	XM_047440080.1	c.-294+1021C>T		intron_variant			XP_047296036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WFDC11	ENST00000324384.4	c.-134+1021C>T		intron_variant		1	NM_147197.2	ENSP00000318753	P1
WFDC11	ENST00000356562.6	c.-134+1025C>T		intron_variant		1		ENSP00000348968	P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26600 AN: 151800 Hom.: 2515 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.175 AC: 26634 AN: 151918 Hom.: 2520 Cov.: 32 AF XY: 0.173 AC XY: 12878 AN XY: 74262

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.166

Alfa AF: 0.167 Hom.: 284

Bravo AF: 0.188

Asia WGS AF: 0.190 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6094192; hg19: chr20-44297796; COSMIC: COSV60976288; COSMIC: COSV60976288;