rs337847

Variant names:

• chr5-78964065-G-A
• rs337847
• NM_000046.5:c.690+351C>T

Variant summary

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

The NM_000046.5(ARSB):​c.690+351C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,246 control chromosomes in the GnomAD database, including 62,072 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 0.90 (62072 hom., cov: 32)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 14 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSB	NM_000046.5	c.690+351C>T		intron_variant	Intron 3 of 7	ENST00000264914.10	NP_000037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSB	ENST00000264914.10	c.690+351C>T		intron_variant	Intron 3 of 7	1	NM_000046.5	ENSP00000264914.4
ARSB	ENST00000396151.7	c.690+351C>T		intron_variant	Intron 4 of 7	1		ENSP00000379455.3
ARSB	ENST00000565165.2	c.690+351C>T		intron_variant	Intron 3 of 4	1		ENSP00000456339.2

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137227 AN: 152128 Hom.: 62010 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.902 AC: 137347 AN: 152246 Hom.: 62072 Cov.: 32 AF XY: 0.902 AC XY: 67179 AN XY: 74438

African (AFR) AF: 0.919 AC: 38168 AN: 41546

American (AMR) AF: 0.893 AC: 13663 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3268 AN: 3472

East Asian (EAS) AF: 0.694 AC: 3591 AN: 5172

South Asian (SAS) AF: 0.841 AC: 4053 AN: 4818

European-Finnish (FIN) AF: 0.936 AC: 9931 AN: 10614

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61661 AN: 68016

Other (OTH) AF: 0.896 AC: 1888 AN: 2108

Alfa AF: 0.902 Hom.: 256785

Bravo AF: 0.901

Asia WGS AF: 0.785 AC: 2731 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.51
DANN	Benign	0.75
PhyloP100		-0.25
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: rs337847; hg19: chr5-78259888;