Variant chr11-6626391-T-C 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 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:7

Conservation

PhyloP100: -3.48

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=-0.93).

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	Protein	UniProt
DCHS1	NM_003737.4 linkuse as main transcript	c.6365-11A>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.6365-11A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003737.4	ENSP00000299441	P1

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52445

AN:

151872

Hom.:

9338

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.367

AC XY:

266506

AN XY:

725504

show subpopulations

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.:

AF XY:

0.345

AC XY:

25662

AN XY:

74296

show subpopulations

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	- -

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

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