11-6621872-G-C

Variant names:

• chr11-6621872-G-C
• rs141839556
• NM_003737.4:c.9804C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_003737.4(DCHS1):​c.9804C>G​(p.Val3268Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,820 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. Synonymous variant affecting the same amino acid position (i.e. V3268V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DCHS1 NM_003737.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.233).
• BP7: Synonymous conserved (PhyloP=0.438 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS1	NM_003737.4	MANE Select	c.9804C>G	p.Val3268Val	synonymous	Exon 21 of 21	NP_003728.1	Q96JQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCHS1	ENST00000299441.5	TSL:1 MANE Select	c.9804C>G	p.Val3268Val	synonymous	Exon 21 of 21	ENSP00000299441.3	Q96JQ0
	DCHS1-AS1	ENST00000526456.1	TSL:4	n.422G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459820 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 725954

African (AFR) AF: 0.0000299 AC: 1 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 85896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111080

Other (OTH) AF: 0.00 AC: 0 AN: 60298

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		0.44

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

Other links and lift over

dbSNP: rs141839556; hg19: chr11-6643103;