5-78980069-G-A

Position:

• chr5-78980069-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000046.5(ARSB):​c.312+4868C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,010 control chromosomes in the GnomAD database, including 13,668 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13668 hom., cov: 33)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSB	NM_000046.5	c.312+4868C>T		intron_variant		ENST00000264914.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSB	ENST00000264914.10	c.312+4868C>T		intron_variant		1	NM_000046.5	P1
ARSB	ENST00000396151.7	c.312+4868C>T		intron_variant		1
ARSB	ENST00000565165.2	c.312+4868C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 64015 AN: 151892 Hom.: 13650 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.422 AC: 64081 AN: 152010 Hom.: 13668 Cov.: 33 AF XY: 0.419 AC XY: 31111 AN XY: 74300

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.416

Alfa AF: 0.409 Hom.: 1540

Bravo AF: 0.426

Asia WGS AF: 0.328 AC: 1140 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.12

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: rs650304; hg19: chr5-78275892; COSMIC: COSV53719844;