Variant 11-6621604-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003737.4(DCHS1):c.*175G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 766,734 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 13 hom., cov: 32)

Exomes 𝑓: 0.011 ( 121 hom. )

Consequence

DCHS1
NM_003737.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.633

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:

DCHS1-AS1 (HGNC:40650): (DCHS1 antisense RNA 1)

DCHS1-AS1 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=-0.81).

BP6

Variant 11-6621604-C-T is Benign according to our data. Variant chr11-6621604-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0103 (1564/152320) while in subpopulation SAS AF= 0.0512 (247/4828). AF 95% confidence interval is 0.0459. There are 13 homozygotes in gnomad4. There are 800 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCHS1	NM_003737.4 linkuse as main transcript	c.*175G>A		3_prime_UTR_variant	21/21	ENST00000299441.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCHS1	ENST00000299441.5 linkuse as main transcript	c.*175G>A		3_prime_UTR_variant	21/21	1	NM_003737.4	P1
DCHS1-AS1	ENST00000526456.1 linkuse as main transcript	n.154C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1563

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.0511

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00808

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.0130

AC:

1769

AN:

135998

Hom.:

AF XY:

0.0153

AC XY:

1126

AN XY:

73770

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.00488

Gnomad ASJ exome

AF:

0.00799

Gnomad EAS exome

AF:

0.000567

Gnomad SAS exome

AF:

0.0447

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00815

Gnomad OTH exome

AF:

0.0102

GnomAD4 exome

AF:

0.0114

AC:

7009

AN:

614414

Hom.:

121

Cov.:

AF XY:

0.0133

AC XY:

4358

AN XY:

328436

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.00559

Gnomad4 ASJ exome

AF:

0.00624

Gnomad4 EAS exome

AF:

0.000248

Gnomad4 SAS exome

AF:

0.0462

Gnomad4 FIN exome

AF:

0.00177

Gnomad4 NFE exome

AF:

0.00821

Gnomad4 OTH exome

AF:

0.0100

GnomAD4 genome

AF:

0.0103

AC:

1564

AN:

152320

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

800

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.00738

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.0512

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00810

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00848

Hom.:

Bravo

AF:

0.00994

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 14, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.8

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

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