18-31386555-G-C

Position:

• chr18-31386555-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177986.5(DSG4):​c.85-133G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 1,344,086 control chromosomes in the GnomAD database, including 378,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39072 hom., cov: 32)
  • Exomes 𝑓: 0.75 (338967 hom.)
• Consequence: DSG4 NM_177986.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.935

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 18-31386555-G-C is Benign according to our data. Variant chr18-31386555-G-C is described in ClinVar as [Benign]. Clinvar id is 1275488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
DSG4	NM_177986.5	c.85-133G>C		intron_variant		ENST00000308128.9	NP_817123.1
DSG4	NM_001134453.3	c.85-133G>C		intron_variant			NP_001127925.1
DSG1-AS1	NR_110788.1	n.157-32102C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSG4	ENST00000308128.9	c.85-133G>C		intron_variant		1	NM_177986.5	ENSP00000311859.4

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107834 AN: 151900 Hom.: 39057 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.740

GnomAD4 exome AF: 0.752 AC: 895877 AN: 1192068 Hom.: 338967 AF XY: 0.749 AC XY: 449487 AN XY: 599860

Gnomad4 AFR exome AF: 0.552

Gnomad4 AMR exome AF: 0.872

Gnomad4 ASJ exome AF: 0.762

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.674

Gnomad4 FIN exome AF: 0.704

Gnomad4 NFE exome AF: 0.755

Gnomad4 OTH exome AF: 0.741

GnomAD4 genome AF: 0.710 AC: 107886 AN: 152018 Hom.: 39072 Cov.: 32 AF XY: 0.710 AC XY: 52721 AN XY: 74304

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.741

Alfa AF: 0.660 Hom.: 2038

Bravo AF: 0.715

Asia WGS AF: 0.745 AC: 2592 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.91
CADD	Benign	0.36
DANN	Benign	0.35

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: rs1460597; hg19: chr18-28966518;