chr18-31342571-T-C

Variant names:

• chr18-31342571-T-C
• rs12969200
• NM_001942.4:c.1688-879T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

DSG1-AS1 (HGNC:51115): (DSG1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DSG1	NM_001942.4	c.1688-879T>C		intron_variant	Intron 11 of 14	ENST00000257192.5	NP_001933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG1	ENST00000257192.5	c.1688-879T>C		intron_variant	Intron 11 of 14	1	NM_001942.4	ENSP00000257192.4
DSG1-AS1	ENST00000812429.1	n.90-14085A>G		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.141 AC: 5860 AN: 41508

American (AMR) AF: 0.234 AC: 3576 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3472

East Asian (EAS) AF: 0.0434 AC: 225 AN: 5180

South Asian (SAS) AF: 0.394 AC: 1901 AN: 4824

European-Finnish (FIN) AF: 0.503 AC: 5287 AN: 10502

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.405 AC: 27500 AN: 67954

Other (OTH) AF: 0.329 AC: 692 AN: 2104

Alfa AF: 0.371 Hom.: 21703

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
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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: rs12969200; hg19: chr18-28922534;