chr18-31330652-A-G

Variant names:

• chr18-31330652-A-G
• rs2199301
• NM_001942.4:c.517+616A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001942.4(DSG1):​c.517+616A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,988 control chromosomes in the GnomAD database, including 14,278 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 0.41 (14278 hom., cov: 32)
• Consequence: DSG1 NM_001942.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSG1	NM_001942.4	c.517+616A>G		intron_variant	Intron 5 of 14	ENST00000257192.5	NP_001933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSG1	ENST00000257192.5	c.517+616A>G		intron_variant	Intron 5 of 14	1	NM_001942.4	ENSP00000257192.4
DSG1-AS1	ENST00000812429.1	n.90-2166T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62962 AN: 151870 Hom.: 14283 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.414 AC: 62974 AN: 151988 Hom.: 14278 Cov.: 32 AF XY: 0.417 AC XY: 30994 AN XY: 74290

African (AFR) AF: 0.306 AC: 12689 AN: 41492

American (AMR) AF: 0.307 AC: 4685 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3468

East Asian (EAS) AF: 0.0584 AC: 303 AN: 5184

South Asian (SAS) AF: 0.483 AC: 2325 AN: 4816

European-Finnish (FIN) AF: 0.590 AC: 6223 AN: 10546

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.496 AC: 33715 AN: 67928

Other (OTH) AF: 0.432 AC: 907 AN: 2100

Alfa AF: 0.469 Hom.: 26329

Bravo AF: 0.384

Asia WGS AF: 0.288 AC: 999 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.60
PhyloP100		-0.32
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: rs2199301; hg19: chr18-28910615;