6-116293138-A-G

Position:

• chr6-116293138-A-G

Variant summary

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

The ENST00000452085.7(DSE):​c.-54+12878A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.978 in 152,306 control chromosomes in the GnomAD database, including 72,917 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 0.98 (72917 hom., cov: 33)
• Consequence: DSE ENST00000452085.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSE	NM_001080976.3	c.-54+12878A>G		intron_variant			NP_001074445.1
DSE	NM_001322937.2	c.-54+34171A>G		intron_variant			NP_001309866.1
DSE	NM_001322938.2	c.-54+34171A>G		intron_variant			NP_001309867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSE	ENST00000452085.7	c.-54+12878A>G		intron_variant		1		ENSP00000404049	P1
DSE	ENST00000449314.5	n.62+12878A>G		intron_variant, non_coding_transcript_variant		1
DSE	ENST00000430252.6	c.-54+34171A>G		intron_variant		2		ENSP00000397597

Frequencies

GnomAD3 genomes AF: 0.978 AC: 148824 AN: 152188 Hom.: 72867 Cov.: 33

Gnomad AFR AF: 0.922

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.985

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

GnomAD4 genome AF: 0.978 AC: 148933 AN: 152306 Hom.: 72917 Cov.: 33 AF XY: 0.979 AC XY: 72924 AN XY: 74482

Gnomad4 AFR AF: 0.922

Gnomad4 AMR AF: 0.993

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.985

Alfa AF: 0.993 Hom.: 4057

Bravo AF: 0.975

Asia WGS AF: 0.996 AC: 3460 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.54

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: rs4326261; hg19: chr6-116614301;