rs11827437

chr11-6626391-T-Cchr11-6626391-T-G

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.6365-11A>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 0.366 in 1,610,880 control chromosomes in the GnomAD database, including 108,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9344 hom., cov: 32)
  • Exomes 𝑓: 0.37 (99496 hom.)
• Consequence: DCHS1 NM_003737.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001206
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.48

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=-0.93).
• BP6: Variant 11-6626391-T-C is Benign according to our data. Variant chr11-6626391-T-C is described in ClinVar as [Benign]. Clinvar id is 259141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6626391-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCHS1	NM_003737.4	c.6365-11A>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.6365-11A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003737.4	P1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52445 AN: 151872 Hom.: 9338 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.361

GnomAD3 exomes AF: 0.365 AC: 89668 AN: 245786 Hom.: 16330 AF XY: 0.364 AC XY: 48312 AN XY: 132772

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.350

Gnomad ASJ exome AF: 0.401

Gnomad EAS exome AF: 0.442

Gnomad SAS exome AF: 0.306

Gnomad FIN exome AF: 0.396

Gnomad NFE exome AF: 0.378

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.368 AC: 537159 AN: 1458888 Hom.: 99496 Cov.: 45 AF XY: 0.367 AC XY: 266506 AN XY: 725504

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.460

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.345 AC: 52471 AN: 151992 Hom.: 9344 Cov.: 32 AF XY: 0.345 AC XY: 25662 AN XY: 74296

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.358

Alfa AF: 0.357 Hom.: 3203

Bravo AF: 0.338

Asia WGS AF: 0.348 AC: 1216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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	- -

Van Maldergem syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.51
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0080
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

Other links and lift over

dbSNP: rs11827437; hg19: chr11-6647622; COSMIC: COSV55037249; COSMIC: COSV55037249;