Variant 22-29073142-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000400335.9(KREMEN1):c.12A>C(p.Pro4Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,088,030 control chromosomes in the GnomAD database, including 266,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 39769 hom., cov: 29)

Exomes 𝑓: 0.69 ( 226469 hom. )

Consequence

KREMEN1
ENST00000400335.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.572

Variant links:

Genes affected

KREMEN1 (HGNC:17550): (kringle containing transmembrane protein 1) This gene encodes a high-affinity dickkopf homolog 1 (DKK1) transmembrane receptor that functionally cooperates with DKK1 to block wingless (WNT)/beta-catenin signaling. The encoded protein is a component of a membrane complex that modulates canonical WNT signaling through lipoprotein receptor-related protein 6 (LRP6). It contains extracellular kringle, WSC, and CUB domains. Mutations in this gene result in ectodermal dysplasia. This protein has also been found to be a functional receptor for Coxsackievirus A10 and may be an alternative entry receptor for SARS-CoV-2. [provided by RefSeq, Nov 2021]

KREMEN1 links:

C22orf31 (HGNC:26931): (chromosome 22 open reading frame 31)

C22orf31 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 22-29073142-A-C is Benign according to our data. Variant chr22-29073142-A-C is described in ClinVar as [Benign]. Clinvar id is 1666871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.572 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KREMEN1	NM_001039570.3 linkuse as main transcript	c.12A>C	p.Pro4Pro	synonymous_variant	1/9	ENST00000400335.9	NP_001034659.2	Q96MU8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KREMEN1	ENST00000400335.9 linkuse as main transcript	c.12A>C	p.Pro4Pro	synonymous_variant	1/9	1	NM_001039570.3	ENSP00000383189.4	Q96MU8-3
KREMEN1	ENST00000407188.5 linkuse as main transcript	c.12A>C	p.Pro4Pro	synonymous_variant	1/9	1		ENSP00000385431.1	Q96MU8-1
KREMEN1	ENST00000327813.9 linkuse as main transcript	c.12A>C	p.Pro4Pro	synonymous_variant	1/10	2		ENSP00000331242.5	Q96MU8-2

Frequencies

GnomAD3 genomes

AF:

0.733

AC:

107432

AN:

146566

Hom.:

39730

Cov.:

show subpopulations

Gnomad AFR

AF:

0.825

Gnomad AMI

AF:

0.750

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.723

Gnomad SAS

AF:

0.684

Gnomad FIN

AF:

0.759

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.696

Gnomad OTH

AF:

0.743

GnomAD3 exomes

AF:

0.515

AC:

1894

AN:

3680

Hom.:

612

AF XY:

0.525

AC XY:

1059

AN XY:

2018

show subpopulations

Gnomad AFR exome

AF:

0.744

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.726

Gnomad EAS exome

AF:

0.500

Gnomad SAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.609

Gnomad NFE exome

AF:

0.614

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.692

AC:

651482

AN:

941358

Hom.:

226469

Cov.:

AF XY:

0.692

AC XY:

309503

AN XY:

447500

show subpopulations

Gnomad4 AFR exome

AF:

0.836

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.798

Gnomad4 EAS exome

AF:

0.736

Gnomad4 SAS exome

AF:

0.664

Gnomad4 FIN exome

AF:

0.715

Gnomad4 NFE exome

AF:

0.689

Gnomad4 OTH exome

AF:

0.697

GnomAD4 genome

AF:

0.733

AC:

107525

AN:

146672

Hom.:

39769

Cov.:

AF XY:

0.733

AC XY:

52303

AN XY:

71400

show subpopulations

Gnomad4 AFR

AF:

0.826

Gnomad4 AMR

AF:

0.629

Gnomad4 ASJ

AF:

0.792

Gnomad4 EAS

AF:

0.724

Gnomad4 SAS

AF:

0.683

Gnomad4 FIN

AF:

0.759

Gnomad4 NFE

AF:

0.696

Gnomad4 OTH

AF:

0.741

Alfa

AF:

0.716

Hom.:

4799

Bravo

AF:

0.733

Asia WGS

AF:

0.674

AC:

2041

AN:

3028

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over