rs180047

chr5-78956699-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSB	NM_000046.5	c.691-1197G>A		intron_variant		ENST00000264914.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSB	ENST00000264914.10	c.691-1197G>A		intron_variant		1	NM_000046.5	P1
ARSB	ENST00000396151.7	c.691-1197G>A		intron_variant		1
ARSB	ENST00000565165.2	c.691-1197G>A		intron_variant		1

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

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.818

Alfa AF: 0.811 Hom.: 17471

Bravo AF: 0.811

Asia WGS AF: 0.662 AC: 2303 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.6
Dann	Benign	0.45

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: rs180047; hg19: chr5-78252522; COSMIC: COSV53721896; COSMIC: COSV53721896;