rs921945

chr5-78966134-A-G

Variant summary

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

The NM_000046.5(ARSB):c.500-1528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,124 control chromosomes in the GnomAD database, including 6,641 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 0.26 (6641 hom., cov: 33)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.536

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSB	NM_000046.5	c.500-1528T>C		intron_variant		ENST00000264914.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSB	ENST00000264914.10	c.500-1528T>C		intron_variant		1	NM_000046.5	P1
ARSB	ENST00000396151.7	c.500-1528T>C		intron_variant		1
ARSB	ENST00000565165.2	c.500-1528T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40210 AN: 152006 Hom.: 6609 Cov.: 33

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.265 AC: 40289 AN: 152124 Hom.: 6641 Cov.: 33 AF XY: 0.260 AC XY: 19328 AN XY: 74386

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.254

Alfa AF: 0.233 Hom.: 2334

Bravo AF: 0.280

Asia WGS AF: 0.236 AC: 821 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	6.3
Dann	Benign	0.43

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: rs921945; hg19: chr5-78261957;