18-31318604-G-A

Position:

• chr18-31318604-G-A

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.48+256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,924 control chromosomes in the GnomAD database, including 12,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (12737 hom., cov: 32)
• Consequence: DSG1 NM_001942.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.925

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=-0.5).
• BP6: Variant 18-31318604-G-A is Benign according to our data. Variant chr18-31318604-G-A is described in ClinVar as [Benign]. Clinvar id is 1236054.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSG1	NM_001942.4	c.48+256G>A		intron_variant		ENST00000257192.5	NP_001933.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG1	ENST00000257192.5	c.48+256G>A		intron_variant		1	NM_001942.4	ENSP00000257192.4

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58261 AN: 151806 Hom.: 12744 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.0585

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.384 AC: 58272 AN: 151924 Hom.: 12737 Cov.: 32 AF XY: 0.387 AC XY: 28714 AN XY: 74260

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.0584

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.411

Alfa AF: 0.456 Hom.: 32767

Bravo AF: 0.351

Asia WGS AF: 0.280 AC: 972 AN: 3476

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.72

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: rs1426311; hg19: chr18-28898567;