rs10458926

chr11-6624877-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003737.4(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 NM_003737.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003436
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.403

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]

ACMG classification

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	UniProt
DCHS1	NM_003737.4	c.7147-9A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000299441.5

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25064 AN: 151972 Hom.: 2263 Cov.: 33

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

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.: 34 AF XY: 0.172 AC XY: 124826 AN XY: 726592

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.: 33 AF XY: 0.165 AC XY: 12272 AN XY: 74328

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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

Other links and lift over

dbSNP: rs10458926; hg19: chr11-6646108; COSMIC: COSV55039816; COSMIC: COSV55039816;