18-31318238-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001942.4(DSG1):c.-63A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,422,986 control chromosomes in the GnomAD database, including 152,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (15934 hom., cov: 32)
  • Exomes 𝑓: 0.45 (136768 hom.)
• Consequence: DSG1 NM_001942.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.185

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 18-31318238-A-G is Benign according to our data. Variant chr18-31318238-A-G is described in ClinVar as [Benign]. Clinvar id is 1260818.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSG1	NM_001942.4	c.-63A>G		5_prime_UTR_variant	1/15	ENST00000257192.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSG1	ENST00000257192.5	c.-63A>G		5_prime_UTR_variant	1/15	1	NM_001942.4	P1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67754 AN: 151888 Hom.: 15937 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.451

GnomAD4 exome AF: 0.454 AC: 577552 AN: 1270980 Hom.: 136768 Cov.: 18 AF XY: 0.458 AC XY: 294270 AN XY: 643108

Gnomad4 AFR exome AF: 0.445

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.0588

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.565

Gnomad4 NFE exome AF: 0.474

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.446 AC: 67776 AN: 152006 Hom.: 15934 Cov.: 32 AF XY: 0.447 AC XY: 33234 AN XY: 74304

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.0583

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.449

Alfa AF: 0.472 Hom.: 3790

Bravo AF: 0.424

Asia WGS AF: 0.295 AC: 1027 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	12
Dann	Benign	0.79

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: rs1834582; hg19: chr18-28898201; COSMIC: COSV57134626;