rs12969200

Positions:

• chr18-31342571-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001942.4(DSG1):​c.1688-879T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,016 control chromosomes in the GnomAD database, including 8,651 homozygotes. 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: 𝑓 0.31 (8651 hom., cov: 32)
• Consequence: DSG1 NM_001942.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.737

Genes affected

DSG1 (HGNC:3048): (desmoglein 1) This gene encodes a member of the desmoglein protein subfamily. Desmogleins, along with desmocollins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmoglein family members on chromosome 18. The encoded protein has been identified as a target of auto-antibodies in the autoimmune skin blistering disease pemphigus foliaceus. Disruption of this gene has also been associated with the skin diseases palmoplantar keratoderma and erythroderma. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG1	NM_001942.4	c.1688-879T>C		intron_variant		ENST00000257192.5	NP_001933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG1	ENST00000257192.5	c.1688-879T>C		intron_variant		1	NM_001942.4	ENSP00000257192	P1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46703 AN: 151898 Hom.: 8654 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.0435

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46689 AN: 152016 Hom.: 8651 Cov.: 32 AF XY: 0.312 AC XY: 23195 AN XY: 74324

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.0434

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.329

Alfa AF: 0.380 Hom.: 16245

Bravo AF: 0.274

Asia WGS AF: 0.236 AC: 820 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.29
DANN	Benign	0.74

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: rs12969200; hg19: chr18-28922534;