5-78886027-T-C

Variant names:

• chr5-78886027-T-C
• rs180049
• NM_000046.5:c.899-200A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000046.5(ARSB):​c.899-200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,004 control chromosomes in the GnomAD database, including 12,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.40 (12646 hom., cov: 32)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0690
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-78886027-T-C is Benign according to our data. Variant chr5-78886027-T-C is described in ClinVar as Benign. ClinVar VariationId is 680475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000046.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSB	NM_000046.5	MANE Select	c.899-200A>G		intron	N/A	NP_000037.2
	ARSB	NM_198709.3		c.899-200A>G		intron	N/A	NP_942002.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSB	ENST00000264914.10	TSL:1 MANE Select	c.899-200A>G		intron	N/A	ENSP00000264914.4
	ARSB	ENST00000396151.7	TSL:1	c.899-200A>G		intron	N/A	ENSP00000379455.3
	ARSB	ENST00000565165.2	TSL:1	c.899-200A>G		intron	N/A	ENSP00000456339.2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61081 AN: 151886 Hom.: 12639 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.402 AC: 61134 AN: 152004 Hom.: 12646 Cov.: 32 AF XY: 0.400 AC XY: 29734 AN XY: 74324

African (AFR) AF: 0.417 AC: 17280 AN: 41430

American (AMR) AF: 0.431 AC: 6583 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1372 AN: 3468

East Asian (EAS) AF: 0.618 AC: 3188 AN: 5156

South Asian (SAS) AF: 0.571 AC: 2749 AN: 4814

European-Finnish (FIN) AF: 0.281 AC: 2976 AN: 10580

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.377 AC: 25647 AN: 67958

Other (OTH) AF: 0.413 AC: 870 AN: 2106

Alfa AF: 0.389 Hom.: 17764

Bravo AF: 0.409

Asia WGS AF: 0.619 AC: 2153 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.36
PhyloP100		-0.069
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: rs180049; hg19: chr5-78181850;