5-78887302-C-G

Variant names:

• chr5-78887302-C-G
• rs10462560
• NM_000046.5:c.899-1475G>C

Variant summary

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

The NM_000046.5(ARSB):​c.899-1475G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 147,940 control chromosomes in the GnomAD database, including 21,835 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 0.52 (21835 hom., cov: 30)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSB	NM_000046.5	c.899-1475G>C		intron_variant	Intron 4 of 7	ENST00000264914.10	NP_000037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSB	ENST00000264914.10	c.899-1475G>C		intron_variant	Intron 4 of 7	1	NM_000046.5	ENSP00000264914.4
ARSB	ENST00000396151.7	c.899-1475G>C		intron_variant	Intron 5 of 7	1		ENSP00000379455.3
ARSB	ENST00000565165.2	c.899-1475G>C		intron_variant	Intron 4 of 4	1		ENSP00000456339.2
ARSB	ENST00000521800.2	n.81-1475G>C		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.521 AC: 76952 AN: 147812 Hom.: 21827 Cov.: 30

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.520 AC: 76986 AN: 147940 Hom.: 21835 Cov.: 30 AF XY: 0.528 AC XY: 38214 AN XY: 72362

African (AFR) AF: 0.262 AC: 9869 AN: 37604

American (AMR) AF: 0.620 AC: 9414 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2075 AN: 3468

East Asian (EAS) AF: 0.443 AC: 2282 AN: 5152

South Asian (SAS) AF: 0.505 AC: 2422 AN: 4796

European-Finnish (FIN) AF: 0.714 AC: 7524 AN: 10540

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41460 AN: 67908

Other (OTH) AF: 0.539 AC: 1120 AN: 2076

Alfa AF: 0.547 Hom.: 3004

Bravo AF: 0.490

Asia WGS AF: 0.444 AC: 1543 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.26
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: rs10462560; hg19: chr5-78183125; COSMIC: COSV53721548;