rs10514114

Variant names:

• chr5-78964835-C-T
• rs10514114
• NM_000046.5:c.500-229G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000046.5(ARSB):​c.500-229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0895 in 151,578 control chromosomes in the GnomAD database, including 1,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.089 (1679 hom., cov: 32)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0410
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-78964835-C-T is Benign according to our data. Variant chr5-78964835-C-T is described in ClinVar as Benign. ClinVar VariationId is 1293779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSB	NM_000046.5	c.500-229G>A		intron_variant	Intron 2 of 7	ENST00000264914.10	NP_000037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSB	ENST00000264914.10	c.500-229G>A		intron_variant	Intron 2 of 7	1	NM_000046.5	ENSP00000264914.4
ARSB	ENST00000396151.7	c.500-229G>A		intron_variant	Intron 3 of 7	1		ENSP00000379455.3
ARSB	ENST00000565165.2	c.500-229G>A		intron_variant	Intron 2 of 4	1		ENSP00000456339.2

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13511 AN: 151462 Hom.: 1662 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0417

Gnomad ASJ AF: 0.0246

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.0821

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00748

Gnomad OTH AF: 0.0704

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

GnomAD4 genome AF: 0.0895 AC: 13563 AN: 151578 Hom.: 1679 Cov.: 32 AF XY: 0.0880 AC XY: 6523 AN XY: 74100

African (AFR) AF: 0.282 AC: 11615 AN: 41212

American (AMR) AF: 0.0416 AC: 634 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0246 AC: 85 AN: 3452

East Asian (EAS) AF: 0.0321 AC: 166 AN: 5178

South Asian (SAS) AF: 0.0797 AC: 381 AN: 4780

European-Finnish (FIN) AF: 0.00142 AC: 15 AN: 10550

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.00749 AC: 508 AN: 67862

Other (OTH) AF: 0.0697 AC: 146 AN: 2096

Alfa AF: 0.0455 Hom.: 1407

Bravo AF: 0.100

Asia WGS AF: 0.0960 AC: 336 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 05, 2018

GeneDx

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	-0.83
CADD	Benign	4.2
DANN	Benign	0.75
PhyloP100		-0.041
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: rs10514114; hg19: chr5-78260658;