rs10514114

Positions:

• chr5-78964835-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
ARSB	NM_000046.5	c.500-229G>A		intron_variant		ENST00000264914.10	NP_000037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSB	ENST00000264914.10	c.500-229G>A		intron_variant		1	NM_000046.5	ENSP00000264914	P1
ARSB	ENST00000396151.7	c.500-229G>A		intron_variant		1		ENSP00000379455
ARSB	ENST00000565165.2	c.500-229G>A		intron_variant		1		ENSP00000456339

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

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0246

Gnomad4 EAS AF: 0.0321

Gnomad4 SAS AF: 0.0797

Gnomad4 FIN AF: 0.00142

Gnomad4 NFE AF: 0.00749

Gnomad4 OTH AF: 0.0697

Alfa AF: 0.0396 Hom.: 248

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs10514114; hg19: chr5-78260658;