rs12967407

Variant names:

• chr18-31333636-C-T
• rs12967407
• NM_001942.4:c.732C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-31333636-C-T
• chr18-31333636-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001942.4(DSG1):​c.732C>T​(p.Gly244Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,613,032 control chromosomes in the GnomAD database, including 182,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14285 hom., cov: 32)
  • Exomes 𝑓: 0.47 (168163 hom.)
• Consequence: DSG1 NM_001942.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.39
• Publications: 20 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 18-31333636-C-T is Benign according to our data. Variant chr18-31333636-C-T is described in ClinVar as Benign. ClinVar VariationId is 402802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001942.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG1	NM_001942.4	MANE Select	c.732C>T	p.Gly244Gly	synonymous	Exon 7 of 15	NP_001933.2	Q02413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSG1	ENST00000257192.5	TSL:1 MANE Select	c.732C>T	p.Gly244Gly	synonymous	Exon 7 of 15	ENSP00000257192.4	Q02413-1
	DSG1-AS1	ENST00000812429.1		n.90-5150G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62953 AN: 151716 Hom.: 14290 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0577

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.432

GnomAD2 exomes AF: 0.422 AC: 105978 AN: 251018 AF XY: 0.438

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.456

Gnomad EAS exome AF: 0.0531

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.504

Gnomad OTH exome AF: 0.462

GnomAD4 exome AF: 0.470 AC: 687150 AN: 1461198 Hom.: 168163 Cov.: 44 AF XY: 0.473 AC XY: 343592 AN XY: 726950

African (AFR) AF: 0.301 AC: 10090 AN: 33468

American (AMR) AF: 0.224 AC: 10020 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 11695 AN: 26116

East Asian (EAS) AF: 0.0573 AC: 2275 AN: 39682

South Asian (SAS) AF: 0.492 AC: 42455 AN: 86250

European-Finnish (FIN) AF: 0.597 AC: 31872 AN: 53408

Middle Eastern (MID) AF: 0.469 AC: 2707 AN: 5768

European-Non Finnish (NFE) AF: 0.494 AC: 548796 AN: 1111418

Other (OTH) AF: 0.451 AC: 27240 AN: 60374

GnomAD4 genome AF: 0.415 AC: 62965 AN: 151834 Hom.: 14285 Cov.: 32 AF XY: 0.417 AC XY: 30979 AN XY: 74204

African (AFR) AF: 0.306 AC: 12675 AN: 41400

American (AMR) AF: 0.307 AC: 4681 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1578 AN: 3464

East Asian (EAS) AF: 0.0576 AC: 298 AN: 5172

South Asian (SAS) AF: 0.483 AC: 2313 AN: 4786

European-Finnish (FIN) AF: 0.591 AC: 6232 AN: 10548

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33738 AN: 67920

Other (OTH) AF: 0.431 AC: 905 AN: 2102

Alfa AF: 0.452 Hom.: 45215

Bravo AF: 0.384

Asia WGS AF: 0.288 AC: 1003 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Palmoplantar keratoderma i, striate, focal, or diffuse (1)
-	-	1	Severe dermatitis-multiple allergies-metabolic wasting syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.18
DANN	Benign	0.57
PhyloP100		-1.4
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12967407; hg19: chr18-28913599; COSMIC: COSV57135633;