Variant rs10458926 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000299441.5(DCHS1):c.7147-9A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,612,860 control chromosomes in the GnomAD database, including 24,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2262 hom., cov: 33)

Exomes 𝑓: 0.17 ( 22362 hom. )

Consequence

DCHS1
ENST00000299441.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003436

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.403

Variant links:

Genes affected

DCHS1 (HGNC:13681): (dachsous cadherin-related 1) This gene is a member of the cadherin superfamily whose members encode calcium-dependent cell-cell adhesion molecules. The encoded protein has a signal peptide, 27 cadherin repeat domains and a unique cytoplasmic region. This particular cadherin family member is expressed in fibroblasts but not in melanocytes or keratinocytes. The cell-cell adhesion of fibroblasts is thought to be necessary for wound healing. [provided by RefSeq, Jul 2008]

DCHS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-6624877-T-C is Benign according to our data. Variant chr11-6624877-T-C is described in ClinVar as [Benign]. Clinvar id is 259142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6624877-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCHS1	NM_003737.4 linkuse as main transcript	c.7147-9A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000299441.5	NP_003728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCHS1	ENST00000299441.5 linkuse as main transcript	c.7147-9A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003737.4	ENSP00000299441	P1

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25064

AN:

151972

Hom.:

2263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.185

AC:

46104

AN:

249544

Hom.:

4587

AF XY:

0.186

AC XY:

25040

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.345

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.171

AC:

249790

AN:

1460768

Hom.:

22362

Cov.:

AF XY:

0.172

AC XY:

124826

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.186

GnomAD4 genome

AF:

0.165

AC:

25073

AN:

152092

Hom.:

2262

Cov.:

AF XY:

0.165

AC XY:

12272

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.350

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.164

Hom.:

643

Bravo

AF:

0.168

Asia WGS

AF:

0.239

AC:

833

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.5

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000034

dbscSNV1_RF

Benign

0.0040

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over