5-78977119-T-C

Variant names:

• chr5-78977119-T-C
• rs2052550
• NM_000046.5:c.312+7818A>G

Variant summary

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

The NM_000046.5(ARSB):​c.312+7818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,692 control chromosomes in the GnomAD database, including 30,980 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 0.61 (30980 hom., cov: 31)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695
• Publications: 16 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSB	NM_000046.5	c.312+7818A>G		intron_variant	Intron 1 of 7	ENST00000264914.10	NP_000037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSB	ENST00000264914.10	c.312+7818A>G		intron_variant	Intron 1 of 7	1	NM_000046.5	ENSP00000264914.4
ARSB	ENST00000396151.7	c.312+7818A>G		intron_variant	Intron 2 of 7	1		ENSP00000379455.3
ARSB	ENST00000565165.2	c.312+7818A>G		intron_variant	Intron 1 of 4	1		ENSP00000456339.2

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92432 AN: 151576 Hom.: 30990 Cov.: 31

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.609 AC: 92427 AN: 151692 Hom.: 30980 Cov.: 31 AF XY: 0.605 AC XY: 44858 AN XY: 74100

African (AFR) AF: 0.336 AC: 13865 AN: 41278

American (AMR) AF: 0.598 AC: 9130 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2455 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2318 AN: 5156

South Asian (SAS) AF: 0.487 AC: 2341 AN: 4806

European-Finnish (FIN) AF: 0.760 AC: 7936 AN: 10438

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52321 AN: 67972

Other (OTH) AF: 0.618 AC: 1301 AN: 2106

Alfa AF: 0.635 Hom.: 22569

Bravo AF: 0.584

Asia WGS AF: 0.473 AC: 1648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.1
DANN	Benign	0.82
PhyloP100		0.69
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: rs2052550; hg19: chr5-78272942;