11-11967604-C-G

Variant names:

• chr11-11967604-C-G
• rs7396187
• NM_001018057.2:c.529-506G>C

Variant summary

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

The NM_001018057.2(DKK3):​c.529-506G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 152,274 control chromosomes in the GnomAD database, including 54,565 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 0.84 (54565 hom., cov: 34)
• Consequence: DKK3 NM_001018057.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK3	NM_001018057.2	c.529-506G>C		intron_variant	Intron 4 of 6	ENST00000683431.1	NP_001018067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK3	ENST00000683431.1	c.529-506G>C		intron_variant	Intron 4 of 6		NM_001018057.2	ENSP00000506835.1

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128352 AN: 152156 Hom.: 54497 Cov.: 34

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.894

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.844 AC: 128478 AN: 152274 Hom.: 54565 Cov.: 34 AF XY: 0.843 AC XY: 62726 AN XY: 74452

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.857

Alfa AF: 0.817 Hom.: 6330

Bravo AF: 0.860

Asia WGS AF: 0.807 AC: 2808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.38
DANN	Benign	0.64

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: rs7396187; hg19: chr11-11989151;