16-84327871-A-G

Variant names:

• chr16-84327871-A-G
• rs3785054
• NM_021197.4:c.*15+916A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021197.4(WFDC1):​c.*15+916A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,048 control chromosomes in the GnomAD database, including 5,939 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 0.28 (5935 hom., cov: 32)
  • Exomes 𝑓: 0.39 (4 hom.)
• Consequence: WFDC1 NM_021197.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021197.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC1	NM_021197.4	MANE Select	c.*15+916A>G		intron	N/A	NP_067020.2
	WFDC1	NM_001282466.2		c.*15+916A>G		intron	N/A	NP_001269395.1
	WFDC1	NM_001282467.2		c.*15+916A>G		intron	N/A	NP_001269396.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC1	ENST00000219454.10	TSL:1 MANE Select	c.*15+916A>G		intron	N/A	ENSP00000219454.5
	WFDC1	ENST00000622779.1	TSL:6	n.2208A>G		non_coding_transcript_exon	Exon 1 of 1
	WFDC1	ENST00000568638.1	TSL:2	c.*15+916A>G		intron	N/A	ENSP00000456920.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42167 AN: 151840 Hom.: 5924 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.389 AC: 35 AN: 90 Hom.: 4 Cov.: 0 AF XY: 0.388 AC XY: 31 AN XY: 80

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.397 AC: 27 AN: 68

Other (OTH) AF: 0.400 AC: 4 AN: 10

GnomAD4 genome AF: 0.278 AC: 42210 AN: 151958 Hom.: 5935 Cov.: 32 AF XY: 0.282 AC XY: 20967 AN XY: 74266

African (AFR) AF: 0.298 AC: 12361 AN: 41450

American (AMR) AF: 0.250 AC: 3819 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.360 AC: 1853 AN: 5152

South Asian (SAS) AF: 0.293 AC: 1410 AN: 4812

European-Finnish (FIN) AF: 0.346 AC: 3651 AN: 10548

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17775 AN: 67938

Other (OTH) AF: 0.253 AC: 534 AN: 2110

Alfa AF: 0.273 Hom.: 706

Bravo AF: 0.272

Asia WGS AF: 0.340 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.30
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3785054; hg19: chr16-84361477;