rs2272960

Positions:

• chr20-45609906-T-C

Variant summary

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

The NM_147198.4(WFDC9):​c.91+185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0456 in 152,220 control chromosomes in the GnomAD database, including 320 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 0.046 (320 hom., cov: 32)
• Consequence: WFDC9 NM_147198.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

Genes affected

WFDC9 (HGNC:20380): (WAP four-disulfide core domain 9) The WAP-type four-disulfide core (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 in many members of the WFDC domain family. This gene encodes a protein which contains a WFDC domain, and is thus a member of the WFDC domain family. This gene and several other gene family members are clustered at 20q13.12. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WFDC9	NM_147198.4	c.91+185A>G		intron_variant		ENST00000326000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WFDC9	ENST00000326000.2	c.91+185A>G		intron_variant		1	NM_147198.4	P1

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6919 AN: 152102 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0456 AC: 6934 AN: 152220 Hom.: 320 Cov.: 32 AF XY: 0.0485 AC XY: 3610 AN XY: 74420

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.0997

Gnomad4 FIN AF: 0.0342

Gnomad4 NFE AF: 0.0173

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0343 Hom.: 28

Bravo AF: 0.0466

Asia WGS AF: 0.199 AC: 691 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	4.7
DANN	Benign	0.67

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: rs2272960; hg19: chr20-44238545;