rs508521

Positions:

• chr6-116426078-A-G
• chr6-116426078-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013352.4(DSE):​c.417-496A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,084 control chromosomes in the GnomAD database, including 39,346 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (39346 hom., cov: 32)
• Consequence: DSE NM_013352.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

Genes affected

DSE (HGNC:21144): (dermatan sulfate epimerase) The protein encoded by this gene is a tumor-rejection antigen. It is localized to the endoplasmic reticulum and functions to convert D-glucuronic acid to L-iduronic acid during the biosynthesis of dermatan sulfate. This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in cancer patients and may be useful for specific immunotherapy. Mutations in this gene cause inmusculocontractural Ehlers-Danlos syndrome. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 9, and a paralogous gene exists on chromosome 18. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DSE	NM_013352.4	c.417-496A>G		intron_variant		ENST00000644252.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DSE	ENST00000644252.3	c.417-496A>G		intron_variant			NM_013352.4	P1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108501 AN: 151966 Hom.: 39306 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.714 AC: 108593 AN: 152084 Hom.: 39346 Cov.: 32 AF XY: 0.711 AC XY: 52842 AN XY: 74322

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.690

Alfa AF: 0.698 Hom.: 50289

Bravo AF: 0.720

Asia WGS AF: 0.515 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.43

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: rs508521; hg19: chr6-116747241;