11-6621791-C-T

Variant names:

• chr11-6621791-C-T
• rs765591706
• NM_003737.4:c.9885G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_Moderate BP7

The NM_003737.4(DCHS1):​c.9885G>A​(p.Glu3295Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000418 in 1,435,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: DCHS1 NM_003737.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06

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 Likely_benign. Variant got -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=3.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCHS1	NM_003737.4	c.9885G>A	p.Glu3295Glu	synonymous_variant	Exon 21 of 21	ENST00000299441.5	NP_003728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCHS1	ENST00000299441.5	c.9885G>A	p.Glu3295Glu	synonymous_variant	Exon 21 of 21	1	NM_003737.4	ENSP00000299441.3
DCHS1-AS1	ENST00000526456.1	n.341C>T		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000485 AC: 1 AN: 205996 Hom.: 0 AF XY: 0.00000900 AC XY: 1 AN XY: 111064

Gnomad AFR exome AF: 0.00

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: 0.0000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000418 AC: 6 AN: 1435638 Hom.: 0 Cov.: 30 AF XY: 0.00000281 AC XY: 2 AN XY: 711512

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000546

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.92

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: rs765591706; hg19: chr11-6643022;