rs11996105

Positions:

• chr8-42381170-G-A
• chr8-42381170-G-C

Variant summary

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

The XM_011544488.3(DKK4):​c.-128+3400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,496 control chromosomes in the GnomAD database, including 6,570 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 0.21 (6570 hom., cov: 31)
• Consequence: DKK4 XM_011544488.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

Genes affected

DKK4 (HGNC:2894): (dickkopf WNT signaling pathway inhibitor 4) 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. Activity of this protein is modulated by binding to the Wnt co-receptor and the co-factor kremen 2. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DKK4	XM_011544488.3	c.-128+3400C>T		intron_variant			XP_011542790.1
DKK4	XM_017013316.2	c.-127-3998C>T		intron_variant			XP_016868805.1
		n.42381170G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31531 AN: 151378 Hom.: 6548 Cov.: 31

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.0518

Gnomad AMR AF: 0.0970

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.209 AC: 31602 AN: 151496 Hom.: 6570 Cov.: 31 AF XY: 0.210 AC XY: 15521 AN XY: 74002

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.0967

Gnomad4 ASJ AF: 0.0582

Gnomad4 EAS AF: 0.0952

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.0652

Gnomad4 OTH AF: 0.162

Alfa AF: 0.0620 Hom.: 129

Bravo AF: 0.218

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.88
DANN	Benign	0.27

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11996105; hg19: chr8-42238688;