Variant rs1569198 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012242.4(DKK1):c.548-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,611,148 control chromosomes in the GnomAD database, including 168,418 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.41 ( 13712 hom., cov: 32)

Exomes 𝑓: 0.45 ( 154706 hom. )

Consequence

DKK1
NM_012242.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.485

Variant links:

Genes affected

DKK1 (HGNC:2891): (dickkopf WNT signaling pathway inhibitor 1) This gene encodes a member of the dickkopf family of proteins. Members of this family are secreted proteins characterized by two cysteine-rich domains that mediate protein-protein interactions. The encoded protein binds to the LRP6 co-receptor and inhibits beta-catenin-dependent Wnt signaling. This gene plays a role in embryonic development and may be important in bone formation in adults. Elevated expression of this gene has been observed in numerous human cancers and this protein may promote proliferation, invasion and growth in cancer cell lines. [provided by RefSeq, Sep 2017]

DKK1 links:

DKK1 (HGNC:):

DKK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DKK1	NM_012242.4 linkuse as main transcript	c.548-43A>G		intron_variant		ENST00000373970.4	NP_036374.1	O94907I1W660

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DKK1	ENST00000373970.4 linkuse as main transcript	c.548-43A>G	intron_variant	1	NM_012242.4	ENSP00000363081.3	O94907
DKK1	ENST00000476752.1 linkuse as main transcript	n.197-43A>G	intron_variant	2
DKK1	ENST00000494277.5 linkuse as main transcript	n.171-43A>G	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

62968

AN:

151910

Hom.:

13708

Cov.:

show subpopulations

Gnomad AFR

AF:

0.312

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.621

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.599

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.414

AC:

103440

AN:

250088

Hom.:

23040

AF XY:

0.416

AC XY:

56179

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.310

Gnomad AMR exome

AF:

0.342

Gnomad ASJ exome

AF:

0.608

Gnomad EAS exome

AF:

0.181

Gnomad SAS exome

AF:

0.317

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.487

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.454

AC:

662238

AN:

1459120

Hom.:

154706

Cov.:

AF XY:

0.452

AC XY:

327607

AN XY:

725484

show subpopulations

Gnomad4 AFR exome

AF:

0.307

Gnomad4 AMR exome

AF:

0.354

Gnomad4 ASJ exome

AF:

0.609

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.321

Gnomad4 FIN exome

AF:

0.452

Gnomad4 NFE exome

AF:

0.477

Gnomad4 OTH exome

AF:

0.451

GnomAD4 genome

AF:

0.414

AC:

62985

AN:

152028

Hom.:

13712

Cov.:

AF XY:

0.411

AC XY:

30541

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.312

Gnomad4 AMR

AF:

0.410

Gnomad4 ASJ

AF:

0.621

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.316

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.484

Gnomad4 OTH

AF:

0.442

Alfa

AF:

0.465

Hom.:

3825

Bravo

AF:

0.409

Asia WGS

AF:

0.227

AC:

793

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.1

DANN

Benign

0.51

BranchPoint Hunter

3.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over