18-31326497-T-C

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.49-84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,088,920 control chromosomes in the GnomAD database, including 123,677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14036 hom., cov: 32)
  • Exomes 𝑓: 0.47 (109641 hom.)
• Consequence: DSG1 NM_001942.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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=-0.85).
• BP6: Variant 18-31326497-T-C is Benign according to our data. Variant chr18-31326497-T-C is described in ClinVar as [Benign]. Clinvar id is 1265775.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSG1	NM_001942.4	c.49-84T>C		intron_variant		ENST00000257192.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSG1	ENST00000257192.5	c.49-84T>C		intron_variant		1	NM_001942.4	P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62405 AN: 151450 Hom.: 14041 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.471 AC: 441773 AN: 937352 Hom.: 109641 AF XY: 0.474 AC XY: 229589 AN XY: 484368

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.0585

Gnomad4 SAS exome AF: 0.492

Gnomad4 FIN exome AF: 0.597

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.412 AC: 62419 AN: 151568 Hom.: 14036 Cov.: 32 AF XY: 0.414 AC XY: 30686 AN XY: 74036

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.0588

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.429

Alfa AF: 0.457 Hom.: 2107

Bravo AF: 0.382

Asia WGS AF: 0.282 AC: 968 AN: 3440

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	-0.85
Cadd	Benign	4.3
Dann	Benign	0.57

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: rs57200666; hg19: chr18-28906460; COSMIC: COSV104377421;