11-11962338-C-T

Variant names:

• chr11-11962338-C-T
• rs1472189
• ENST00000396505.7:c.*2126G>A

Variant summary

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

The ENST00000396505.7(DKK3):​c.*2126G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,046 control chromosomes in the GnomAD database, including 5,474 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 0.25 (5474 hom., cov: 32)
• Consequence: DKK3 ENST00000396505.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 16 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000396505.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK3	ENST00000396505.7	TSL:1	c.*2126G>A		3_prime_UTR	Exon 8 of 8	ENSP00000379762.2	Q9UBP4
	DKK3	ENST00000958793.1		c.*2126G>A		3_prime_UTR	Exon 7 of 7	ENSP00000628852.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37853 AN: 151928 Hom.: 5476 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.249 AC: 37853 AN: 152046 Hom.: 5474 Cov.: 32 AF XY: 0.250 AC XY: 18544 AN XY: 74294

African (AFR) AF: 0.103 AC: 4259 AN: 41516

American (AMR) AF: 0.251 AC: 3836 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1126 AN: 3468

East Asian (EAS) AF: 0.178 AC: 918 AN: 5148

South Asian (SAS) AF: 0.254 AC: 1224 AN: 4818

European-Finnish (FIN) AF: 0.332 AC: 3507 AN: 10550

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22022 AN: 67954

Other (OTH) AF: 0.281 AC: 594 AN: 2112

Alfa AF: 0.292 Hom.: 9930

Bravo AF: 0.241

Asia WGS AF: 0.227 AC: 786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.65
PhyloP100		-0.36

Splicing

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

Other links and lift over

dbSNP: rs1472189; hg19: chr11-11983885;