18-31377109-A-T

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.48+150A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 894,358 control chromosomes in the GnomAD database, including 1,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (353 hom., cov: 32)
  • Exomes 𝑓: 0.057 (1605 hom.)
• Consequence: DSG4 NM_177986.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.532

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=-0.85).
• BP6: Variant 18-31377109-A-T is Benign according to our data. Variant chr18-31377109-A-T is described in ClinVar as [Benign]. Clinvar id is 1241012.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSG4	NM_177986.5	c.48+150A>T		intron_variant		ENST00000308128.9
DSG1-AS1	NR_110788.1	n.157-22656T>A		intron_variant, non_coding_transcript_variant
DSG4	NM_001134453.3	c.48+150A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSG4	ENST00000308128.9	c.48+150A>T		intron_variant		1	NM_177986.5	P2
DSG1-AS1	ENST00000581856.5	n.96-22656T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10166 AN: 152054 Hom.: 352 Cov.: 32

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.0507

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0675

GnomAD4 exome AF: 0.0570 AC: 42299 AN: 742186 Hom.: 1605 AF XY: 0.0594 AC XY: 22957 AN XY: 386532

Gnomad4 AFR exome AF: 0.0834

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.0442

Gnomad4 EAS exome AF: 0.0720

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0470

Gnomad4 NFE exome AF: 0.0476

Gnomad4 OTH exome AF: 0.0533

GnomAD4 genome AF: 0.0669 AC: 10183 AN: 152172 Hom.: 353 Cov.: 32 AF XY: 0.0670 AC XY: 4985 AN XY: 74426

Gnomad4 AFR AF: 0.0867

Gnomad4 AMR AF: 0.0844

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.0510

Gnomad4 SAS AF: 0.0874

Gnomad4 FIN AF: 0.0462

Gnomad4 NFE AF: 0.0551

Gnomad4 OTH AF: 0.0659

Alfa AF: 0.0643 Hom.: 44

Bravo AF: 0.0716

Asia WGS AF: 0.0610 AC: 213 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	-0.85
Cadd	Benign	2.6
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: rs10502570; hg19: chr18-28957072;