11-6621604-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.633

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 -14 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_single_submitter, 1 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 GnomAd at 13 AD,AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1563 AN: 152202 Hom.: 13 Cov.: 32

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.: 28 AF XY: 0.0153 AC XY: 1126 AN XY: 73770

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.: 8 AF XY: 0.0133 AC XY: 4358 AN XY: 328436

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.: 13 Cov.: 32 AF XY: 0.0107 AC XY: 800 AN XY: 74484

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.: 2

Bravo AF: 0.00994

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 14, 2019

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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

Other links and lift over

dbSNP: rs77307773; hg19: chr11-6642835;