Variant rs3733895 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000046.5(ARSB):c.313-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,611,296 control chromosomes in the GnomAD database, including 101,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7526 hom., cov: 32)

Exomes 𝑓: 0.35 ( 93571 hom. )

Consequence

ARSB
NM_000046.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.401

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 links:

ARSB (HGNC:):

ARSB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 5-78969218-A-G is Benign according to our data. Variant chr5-78969218-A-G is described in ClinVar as [Benign]. Clinvar id is 254739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-78969218-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSB	NM_000046.5 linkuse as main transcript	c.313-26T>C		intron_variant		ENST00000264914.10	NP_000037.2	P15848-1A0A024RAJ9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ARSB	ENST00000264914.10 linkuse as main transcript	c.313-26T>C	intron_variant	1	NM_000046.5	ENSP00000264914.4	P15848-1
ARSB	ENST00000396151.7 linkuse as main transcript	c.313-26T>C	intron_variant	1		ENSP00000379455.3	P15848-2
ARSB	ENST00000565165.2 linkuse as main transcript	c.313-26T>C	intron_variant	1		ENSP00000456339.2	A0A2U3U034

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45813

AN:

151976

Hom.:

7521

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.360

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.328

GnomAD3 exomes

AF:

0.324

AC:

80995

AN:

250196

Hom.:

13709

AF XY:

0.325

AC XY:

44094

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.296

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.216

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.379

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.354

AC:

516648

AN:

1459202

Hom.:

93571

Cov.:

AF XY:

0.353

AC XY:

256015

AN XY:

726150

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.402

Gnomad4 EAS exome

AF:

0.258

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.381

Gnomad4 NFE exome

AF:

0.371

Gnomad4 OTH exome

AF:

0.339

GnomAD4 genome

AF:

0.301

AC:

45840

AN:

152094

Hom.:

7526

Cov.:

AF XY:

0.301

AC XY:

22414

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.161

Gnomad4 AMR

AF:

0.316

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.267

Gnomad4 FIN

AF:

0.386

Gnomad4 NFE

AF:

0.371

Gnomad4 OTH

AF:

0.328

Alfa

AF:

0.356

Hom.:

20537

Bravo

AF:

0.291

Asia WGS

AF:

0.251

AC:

874

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 22, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Mucopolysaccharidosis type 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over