rs7104941

Variant names:

• chr11-11999069-C-T
• rs7104941
• NM_001018057.2:c.352-290G>A

Variant summary

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

The NM_001018057.2(DKK3):​c.352-290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,034 control chromosomes in the GnomAD database, including 4,177 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 0.22 (4177 hom., cov: 32)
• Consequence: DKK3 NM_001018057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 3 publications found

Genes affected

DKK3 (HGNC:2893): (dickkopf WNT signaling pathway inhibitor 3) This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

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 (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK3	NM_001018057.2	c.352-290G>A		intron_variant	Intron 2 of 6	ENST00000683431.1	NP_001018067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK3	ENST00000683431.1	c.352-290G>A		intron_variant	Intron 2 of 6		NM_001018057.2	ENSP00000506835.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33606 AN: 151916 Hom.: 4164 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0857

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.221 AC: 33650 AN: 152034 Hom.: 4177 Cov.: 32 AF XY: 0.221 AC XY: 16408 AN XY: 74336

African (AFR) AF: 0.309 AC: 12813 AN: 41414

American (AMR) AF: 0.314 AC: 4803 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3470

East Asian (EAS) AF: 0.0861 AC: 445 AN: 5170

South Asian (SAS) AF: 0.250 AC: 1202 AN: 4810

European-Finnish (FIN) AF: 0.129 AC: 1368 AN: 10582

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11719 AN: 67984

Other (OTH) AF: 0.210 AC: 444 AN: 2112

Alfa AF: 0.207 Hom.: 5221

Bravo AF: 0.237

Asia WGS AF: 0.174 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.63
PhyloP100		-0.85
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: rs7104941; hg19: chr11-12020616;