rs2052550

chr5-78977119-T-C

Variant summary

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

The NM_000046.5(ARSB):c.312+7818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,692 control chromosomes in the GnomAD database, including 30,980 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 0.61 (30980 hom., cov: 31)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

Genes affected

ARSB (HGNC:714): (arylsulfatase B) Arylsulfatase B encoded by this gene belongs to the sulfatase family. The arylsulfatase B homodimer hydrolyzes sulfate groups of N-Acetyl-D-galactosamine, chondriotin sulfate, and dermatan sulfate. The protein is targeted to the lysozyme. Mucopolysaccharidosis type VI is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSB	NM_000046.5	c.312+7818A>G		intron_variant		ENST00000264914.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSB	ENST00000264914.10	c.312+7818A>G		intron_variant		1	NM_000046.5	P1
ARSB	ENST00000396151.7	c.312+7818A>G		intron_variant		1
ARSB	ENST00000565165.2	c.312+7818A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92432 AN: 151576 Hom.: 30990 Cov.: 31

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.609 AC: 92427 AN: 151692 Hom.: 30980 Cov.: 31 AF XY: 0.605 AC XY: 44858 AN XY: 74100

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.618

Alfa AF: 0.678 Hom.: 14132

Bravo AF: 0.584

Asia WGS AF: 0.473 AC: 1648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	9.1
Dann	Benign	0.82

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: rs2052550; hg19: chr5-78272942;