5-78814709-C-T

Variant names:

• chr5-78814709-C-T
• rs6453417
• NM_000046.5:c.1213+24647G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000046.5(ARSB):​c.1213+24647G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 150,266 control chromosomes in the GnomAD database, including 26,633 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 0.57 (26633 hom., cov: 32)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 7 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000046.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSB	NM_000046.5	MANE Select	c.1213+24647G>A		intron	N/A	NP_000037.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSB	ENST00000264914.10	TSL:1 MANE Select	c.1213+24647G>A		intron	N/A	ENSP00000264914.4	P15848-1
	ARSB	ENST00000934338.1		c.1186+24647G>A		intron	N/A	ENSP00000604397.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 85992 AN: 150154 Hom.: 26577 Cov.: 32

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.573 AC: 86111 AN: 150266 Hom.: 26633 Cov.: 32 AF XY: 0.575 AC XY: 42199 AN XY: 73414

African (AFR) AF: 0.707 AC: 28615 AN: 40496

American (AMR) AF: 0.537 AC: 8115 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1519 AN: 3466

East Asian (EAS) AF: 0.379 AC: 1932 AN: 5104

South Asian (SAS) AF: 0.611 AC: 2920 AN: 4782

European-Finnish (FIN) AF: 0.580 AC: 6087 AN: 10500

Middle Eastern (MID) AF: 0.479 AC: 139 AN: 290

European-Non Finnish (NFE) AF: 0.520 AC: 35129 AN: 67528

Other (OTH) AF: 0.549 AC: 1140 AN: 2078

Alfa AF: 0.529 Hom.: 38397

Bravo AF: 0.574

Asia WGS AF: 0.553 AC: 1910 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.19
DANN	Benign	0.56
PhyloP100		-1.0
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: rs6453417; hg19: chr5-78110532;