5-78886027-T-C

Position:

• chr5-78886027-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000046.5(ARSB):​c.899-200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,004 control chromosomes in the GnomAD database, including 12,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.40 (12646 hom., cov: 32)
• Consequence: ARSB NM_000046.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0690

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-78886027-T-C is Benign according to our data. Variant chr5-78886027-T-C is described in ClinVar as [Benign]. Clinvar id is 680475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSB	NM_000046.5	c.899-200A>G		intron_variant		ENST00000264914.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSB	ENST00000264914.10	c.899-200A>G		intron_variant		1	NM_000046.5	P1
ARSB	ENST00000396151.7	c.899-200A>G		intron_variant		1
ARSB	ENST00000565165.2	c.899-200A>G		intron_variant		1
ARSB	ENST00000521800.2	n.81-200A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61081 AN: 151886 Hom.: 12639 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.402 AC: 61134 AN: 152004 Hom.: 12646 Cov.: 32 AF XY: 0.400 AC XY: 29734 AN XY: 74324

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.413

Alfa AF: 0.384 Hom.: 11271

Bravo AF: 0.409

Asia WGS AF: 0.619 AC: 2153 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.36

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: rs180049; hg19: chr5-78181850;