rs6870443

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000046.5(ARSB):c.691-22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,596,616 control chromosomes in the GnomAD database, including 25,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1757 hom., cov: 33)

Exomes 𝑓: 0.18 ( 23926 hom. )

Consequence

ARSB
NM_000046.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.381

Publications

6 publications found

Variant links:

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

ARSB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 5-78955524-A-G is Benign according to our data. Variant chr5-78955524-A-G is described in ClinVar as Benign. ClinVar VariationId is 254740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSB	NM_000046.5 link	c.691-22T>C		intron_variant	Intron 3 of 7	ENST00000264914.10	NP_000037.2	P15848-1A0A024RAJ9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARSB	ENST00000264914.10 link	c.691-22T>C	intron_variant	Intron 3 of 7	1	NM_000046.5	ENSP00000264914.4	P15848-1
ARSB	ENST00000396151.7 link	c.691-22T>C	intron_variant	Intron 4 of 7	1		ENSP00000379455.3	P15848-2
ARSB	ENST00000565165.2 link	c.691-22T>C	intron_variant	Intron 3 of 4	1		ENSP00000456339.2	A0A2U3U034
ARSB	ENST00000521800.2 link	n.-150T>C	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21618

AN:

152104

Hom.:

1754

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0736

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.0773

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.157

GnomAD2 exomes

AF:

0.168

AC:

41994

AN:

250604

AF XY:

0.175

show subpopulations

Gnomad AFR exome

AF:

0.0703

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.267

Gnomad EAS exome

AF:

0.0807

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.178

AC:

256610

AN:

1444394

Hom.:

23926

Cov.:

AF XY:

0.180

AC XY:

129611

AN XY:

719760

show subpopulations

African (AFR)

AF:

0.0682

AC:

2254

AN:

33036

American (AMR)

AF:

0.146

AC:

6545

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

7062

AN:

26038

East Asian (EAS)

AF:

0.0624

AC:

2472

AN:

39588

South Asian (SAS)

AF:

0.225

AC:

19331

AN:

85840

European-Finnish (FIN)

AF:

0.116

AC:

6215

AN:

53378

Middle Eastern (MID)

AF:

0.233

AC:

1257

AN:

5406

European-Non Finnish (NFE)

AF:

0.183

AC:

201171

AN:

1096714

Other (OTH)

AF:

0.173

AC:

10303

AN:

59714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

10390

20781

31171

41562

51952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6966

13932

20898

27864

34830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.142

AC:

21622

AN:

152222

Hom.:

1757

Cov.:

AF XY:

0.139

AC XY:

10352

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0734

AC:

3050

AN:

41536

American (AMR)

AF:

0.142

AC:

2171

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

935

AN:

3470

East Asian (EAS)

AF:

0.0779

AC:

404

AN:

5188

South Asian (SAS)

AF:

0.211

AC:

1019

AN:

4818

European-Finnish (FIN)

AF:

0.108

AC:

1149

AN:

10610

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.182

AC:

12382

AN:

67994

Other (OTH)

AF:

0.155

AC:

328

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

965

1929

2894

3858

4823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.179

Hom.:

1160

Bravo

AF:

0.141

Asia WGS

AF:

0.131

AC:

454

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 22, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mucopolysaccharidosis type 6

Benign:2

Jun 19, 2021

Pars Genome Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 01, 2018

Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

Allele frequency greater than 5% in ExAC (BA1) -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.2

(source)

DANN

Benign

0.75

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over