rs13184587

Positions:

• chr5-78910960-G-A
• chr5-78910960-G-T

Variant summary

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

The NM_000046.5(ARSB):​c.899-25133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,982 control chromosomes in the GnomAD database, including 4,525 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 0.23 (4525 hom., cov: 32)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSB	NM_000046.5	c.899-25133C>T		intron_variant		ENST00000264914.10	NP_000037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSB	ENST00000264914.10	c.899-25133C>T		intron_variant		1	NM_000046.5	ENSP00000264914	P1
ARSB	ENST00000396151.7	c.899-25133C>T		intron_variant		1		ENSP00000379455
ARSB	ENST00000565165.2	c.899-25133C>T		intron_variant		1		ENSP00000456339
ARSB	ENST00000521800.2	n.81-25133C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34912 AN: 151864 Hom.: 4526 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.230 AC: 34909 AN: 151982 Hom.: 4525 Cov.: 32 AF XY: 0.236 AC XY: 17542 AN XY: 74290

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.230

Alfa AF: 0.262 Hom.: 5006

Bravo AF: 0.223

Asia WGS AF: 0.163 AC: 566 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.70

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: rs13184587; hg19: chr5-78206783; COSMIC: COSV53729024;