18-31384897-T-C

Variant summary

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

The NM_177986.5(DSG4):c.49-239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,032 control chromosomes in the GnomAD database, including 38,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.70 (38303 hom., cov: 32)
• Consequence: DSG4 NM_177986.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.355

Genes affected

DSG4 (HGNC:21307): (desmoglein 4) This gene encodes a member of the desmoglein subgroup of desmosomal cadherins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a transmembrane component of desmosomes and may play a role in cell-cell adhesion in epithelial cells. Mutations in the gene are associated with localized autosomal recessive hypotrichosis and monilethrix, characterized by impaired hair growth. [provided by RefSeq, May 2016]

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 18-31384897-T-C is Benign according to our data. Variant chr18-31384897-T-C is described in ClinVar as [Benign]. Clinvar id is 1231139.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSG4	NM_177986.5	c.49-239T>C		intron_variant		ENST00000308128.9
DSG1-AS1	NR_110788.1	n.157-30444A>G		intron_variant, non_coding_transcript_variant
DSG4	NM_001134453.3	c.49-239T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSG4	ENST00000308128.9	c.49-239T>C		intron_variant		1	NM_177986.5	P2
DSG1-AS1	ENST00000581856.5	n.96-30444A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106386 AN: 151914 Hom.: 38292 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.700 AC: 106435 AN: 152032 Hom.: 38303 Cov.: 32 AF XY: 0.700 AC XY: 52024 AN XY: 74310

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.821

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.734

Alfa AF: 0.745 Hom.: 9000

Bravo AF: 0.704

Asia WGS AF: 0.742 AC: 2585 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

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.28
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1813419; hg19: chr18-28964860;