rs180047

Variant names:

• chr5-78956699-C-T
• rs180047
• NM_000046.5:c.691-1197G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000046.5(ARSB):​c.691-1197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,102 control chromosomes in the GnomAD database, including 50,096 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 0.81 (50096 hom., cov: 31)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 8 publications found

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]

ARSB Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Illumina, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 = 0.832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000046.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSB	NM_000046.5	MANE Select	c.691-1197G>A		intron	N/A	NP_000037.2
	ARSB	NM_198709.3		c.691-1197G>A		intron	N/A	NP_942002.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSB	ENST00000264914.10	TSL:1 MANE Select	c.691-1197G>A		intron	N/A	ENSP00000264914.4
	ARSB	ENST00000396151.7	TSL:1	c.691-1197G>A		intron	N/A	ENSP00000379455.3
	ARSB	ENST00000565165.2	TSL:1	c.691-1197G>A		intron	N/A	ENSP00000456339.2

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123052 AN: 151984 Hom.: 50040 Cov.: 31

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.810 AC: 123169 AN: 152102 Hom.: 50096 Cov.: 31 AF XY: 0.811 AC XY: 60321 AN XY: 74352

African (AFR) AF: 0.839 AC: 34798 AN: 41470

American (AMR) AF: 0.823 AC: 12594 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3010 AN: 3472

East Asian (EAS) AF: 0.544 AC: 2809 AN: 5160

South Asian (SAS) AF: 0.746 AC: 3597 AN: 4824

European-Finnish (FIN) AF: 0.859 AC: 9100 AN: 10592

Middle Eastern (MID) AF: 0.839 AC: 245 AN: 292

European-Non Finnish (NFE) AF: 0.802 AC: 54523 AN: 67974

Other (OTH) AF: 0.818 AC: 1725 AN: 2108

Alfa AF: 0.803 Hom.: 29230

Bravo AF: 0.811

Asia WGS AF: 0.662 AC: 2303 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		-0.12
Mutation Taster		=100/0	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: rs180047; hg19: chr5-78252522; COSMIC: COSV53721896; COSMIC: COSV53721896;