11-6621842-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_003737.4(DCHS1):c.9834A>G(p.Ser3278=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000505 in 1,610,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00052 (0 hom.)
• Consequence: DCHS1 NM_003737.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.258

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

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 11-6621842-T-C is Benign according to our data. Variant chr11-6621842-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 770971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.258 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000368 (56/152270) while in subpopulation NFE AF= 0.000706 (48/68018). AF 95% confidence interval is 0.000547. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCHS1	NM_003737.4	c.9834A>G	p.Ser3278=	synonymous_variant	21/21	ENST00000299441.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCHS1	ENST00000299441.5	c.9834A>G	p.Ser3278=	synonymous_variant	21/21	1	NM_003737.4	P1
DCHS1-AS1	ENST00000526456.1	n.392T>C		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152152 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000323 AC: 78 AN: 241648 Hom.: 0 AF XY: 0.000320 AC XY: 42 AN XY: 131046

Gnomad AFR exome AF: 0.000134

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000686

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.000519 AC: 757 AN: 1458074 Hom.: 0 Cov.: 31 AF XY: 0.000532 AC XY: 386 AN XY: 724926

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000656

Gnomad4 OTH exome AF: 0.000382

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152270 Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27 AN XY: 74456

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000492 Hom.: 0

Bravo AF: 0.000314

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 06, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2022	DCHS1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	14
Dann	Benign	0.82

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

Other links and lift over

dbSNP: rs201436786; hg19: chr11-6643073;