rs1558875

Positions:

• chr17-68348275-T-C

Variant summary

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

The NM_001267727.2(ARSG):​c.454+1103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,968 control chromosomes in the GnomAD database, including 17,641 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 0.48 (17641 hom., cov: 31)
• Consequence: ARSG NM_001267727.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

Genes affected

ARSG (HGNC:24102): (arylsulfatase G) The protein encoded by this gene belongs to the sulfatase enzyme family. Sulfatases hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules. This protein displays arylsulfatase activity at acidic pH, as is typical of lysosomal sulfatases, and has been shown to localize in the lysosomes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSG	NM_001267727.2	c.454+1103T>C		intron_variant		ENST00000621439.5	NP_001254656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSG	ENST00000621439.5	c.454+1103T>C		intron_variant		5	NM_001267727.2	ENSP00000480910	P1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72258 AN: 151850 Hom.: 17638 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.476 AC: 72286 AN: 151968 Hom.: 17641 Cov.: 31 AF XY: 0.472 AC XY: 35055 AN XY: 74272

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.476

Alfa AF: 0.522 Hom.: 35128

Bravo AF: 0.477

Asia WGS AF: 0.333 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.86

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: rs1558875; hg19: chr17-66344416;