5-78839378-C-T

Position:

chr5-78839378-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000046.5(ARSB):c.1191G>A(p.Pro397=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,612,794 control chromosomes in the GnomAD database, including 35,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 7001 hom., cov: 32)

Exomes 𝑓: 0.18 ( 28451 hom. )

Consequence

ARSB
NM_000046.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 5-78839378-C-T is Benign according to our data. Variant chr5-78839378-C-T is described in ClinVar as [Benign]. Clinvar id is 92354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-78839378-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 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.1191G>A	p.Pro397=	synonymous_variant	6/8	ENST00000264914.10	NP_000037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSB	ENST00000264914.10 linkuse as main transcript	c.1191G>A	p.Pro397=	synonymous_variant	6/8	1	NM_000046.5	ENSP00000264914	P1	P15848-1
ARSB	ENST00000396151.7 linkuse as main transcript	c.1191G>A	p.Pro397=	synonymous_variant	7/8	1		ENSP00000379455		P15848-2

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39800

AN:

151840

Hom.:

6979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.0416

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.257

GnomAD3 exomes

AF:

0.190

AC:

47785

AN:

251354

Hom.:

6033

AF XY:

0.191

AC XY:

25928

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.519

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.271

Gnomad EAS exome

AF:

0.0436

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.185

AC:

269562

AN:

1460836

Hom.:

28451

Cov.:

AF XY:

0.186

AC XY:

135054

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.518

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.0331

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.179

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.262

AC:

39870

AN:

151958

Hom.:

7001

Cov.:

AF XY:

0.257

AC XY:

19069

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.502

Gnomad4 AMR

AF:

0.173

Gnomad4 ASJ

AF:

0.270

Gnomad4 EAS

AF:

0.0419

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.255

Alfa

AF:

0.203

Hom.:

8379

Bravo

AF:

0.276

Asia WGS

AF:

0.157

AC:

547

AN:

3476

EpiCase

AF:

0.201

EpiControl

AF:

0.204

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mucopolysaccharidosis type 6

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jun 19, 2021	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Apr 12, 2017	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 13, 2014	- -
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

-0.74

CADD

Benign

4.4

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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