NM_003737.4:c.7147-9A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003737.4(DCHS1):c.7147-9A>G variant causes a 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 intron

Scores

Splicing: ADA: 0.00003436

Clinical Significance

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

Conservation

PhyloP100: -0.403

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

mitral valve prolapse, myxomatous 2
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
van Maldergem syndrome 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
familial mitral valve prolapse
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
van Maldergem syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DCHS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 259142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003737.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS1	NM_003737.4	MANE Select	c.7147-9A>G		intron	N/A	NP_003728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS1	ENST00000299441.5	TSL:1 MANE Select	c.7147-9A>G		intron	N/A	ENSP00000299441.3

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

GnomAD2 exomes

AF:

0.185

AC:

46104

AN:

249544

AF XY:

0.186

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 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

African (AFR)

AF:

0.115

AC:

3866

AN:

33476

American (AMR)

AF:

0.176

AC:

7830

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

6155

AN:

26120

East Asian (EAS)

AF:

0.341

AC:

13512

AN:

39664

South Asian (SAS)

AF:

0.182

AC:

15693

AN:

86148

European-Finnish (FIN)

AF:

0.143

AC:

7601

AN:

53312

Middle Eastern (MID)

AF:

0.241

AC:

1388

AN:

5762

European-Non Finnish (NFE)

AF:

0.164

AC:

182539

AN:

1111350

Other (OTH)

AF:

0.186

AC:

11206

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

11023

22047

33070

44094

55117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6506

13012

19518

26024

32530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.165

AC:

25073

AN:

152092

Hom.:

2262

Cov.:

AF XY:

0.165

AC XY:

12272

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.117

AC:

4856

AN:

41498

American (AMR)

AF:

0.199

AC:

3048

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

848

AN:

3470

East Asian (EAS)

AF:

0.350

AC:

1798

AN:

5138

South Asian (SAS)

AF:

0.193

AC:

928

AN:

4818

European-Finnish (FIN)

AF:

0.136

AC:

1444

AN:

10592

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11544

AN:

67980

Other (OTH)

AF:

0.180

AC:

378

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1071

2141

3212

4282

5353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.5

(source)

DANN

Benign

0.56

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over