rs6870443

chr5-78955524-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000046.5(ARSB):c.691-22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,596,616 control chromosomes in the GnomAD database, including 25,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1757 hom., cov: 33)
  • Exomes 𝑓: 0.18 (23926 hom.)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.381

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-78955524-A-G is Benign according to our data. Variant chr5-78955524-A-G is described in ClinVar as [Benign]. Clinvar id is 254740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-78955524-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSB	NM_000046.5	c.691-22T>C		intron_variant		ENST00000264914.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSB	ENST00000264914.10	c.691-22T>C		intron_variant		1	NM_000046.5	P1
ARSB	ENST00000396151.7	c.691-22T>C		intron_variant		1
ARSB	ENST00000565165.2	c.691-22T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21618 AN: 152104 Hom.: 1754 Cov.: 33

Gnomad AFR AF: 0.0736

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.157

GnomAD3 exomes AF: 0.168 AC: 41994 AN: 250604 Hom.: 4002 AF XY: 0.175 AC XY: 23772 AN XY: 135498

Gnomad AFR exome AF: 0.0703

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.0807

Gnomad SAS exome AF: 0.226

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.178 AC: 256610 AN: 1444394 Hom.: 23926 Cov.: 28 AF XY: 0.180 AC XY: 129611 AN XY: 719760

Gnomad4 AFR exome AF: 0.0682

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.0624

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.142 AC: 21622 AN: 152222 Hom.: 1757 Cov.: 33 AF XY: 0.139 AC XY: 10352 AN XY: 74434

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0779

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.155

Alfa AF: 0.186 Hom.: 831

Bravo AF: 0.141

Asia WGS AF: 0.131 AC: 454 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mucopolysaccharidosis type 6 Benign:2

Benign, criteria provided, single submitter	curation	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	Jan 01, 2018	Allele frequency greater than 5% in ExAC (BA1) -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 19, 2021	- -

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.2
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6870443; hg19: chr5-78251347; COSMIC: COSV53730949; COSMIC: COSV53730949;