Variant 5-78955524-A-G 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.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

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:

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

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/exons	MANE	Protein	UniProt
ARSB	NM_000046.5 linkuse as main transcript	c.691-22T>C		intron_variant		ENST00000264914.10	NP_000037.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ARSB	ENST00000264914.10 linkuse as main transcript	c.691-22T>C	intron_variant	1	NM_000046.5	ENSP00000264914	P1	P15848-1
ARSB	ENST00000396151.7 linkuse as main transcript	c.691-22T>C	intron_variant	1		ENSP00000379455		P15848-2
ARSB	ENST00000565165.2 linkuse as main transcript	c.691-22T>C	intron_variant	1		ENSP00000456339

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

GnomAD3 exomes

AF:

0.168

AC:

41994

AN:

250604

Hom.:

4002

AF XY:

0.175

AC XY:

23772

AN XY:

135498

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 SAS exome

AF:

0.226

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

Gnomad4 AFR exome

AF:

0.0682

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.0624

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.142

AC:

21622

AN:

152222

Hom.:

1757

Cov.:

AF XY:

0.139

AC XY:

10352

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0734

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.0779

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.186

Hom.:

831

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

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

Mucopolysaccharidosis type 6

Benign:2

Benign, criteria provided, single submitter	curation	Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	Jan 01, 2018	Allele frequency greater than 5% in ExAC (BA1) -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 19, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.2

DANN

Benign

0.75

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

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