rs12945290

Positions:

• chr17-68382856-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.983-2208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,212 control chromosomes in the GnomAD database, including 1,160 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 0.12 (1160 hom., cov: 32)
• Consequence: ARSG NM_001267727.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARSG	NM_001267727.2	c.983-2208T>C		intron_variant		ENST00000621439.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARSG	ENST00000621439.5	c.983-2208T>C		intron_variant		5	NM_001267727.2	P1
ARSG	ENST00000448504.6	c.983-2208T>C		intron_variant		1		P1
ARSG	ENST00000452479.6	c.491-2208T>C		intron_variant		5
ARSG	ENST00000582154.5	n.741-2208T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17620 AN: 152094 Hom.: 1147 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.116 AC: 17656 AN: 152212 Hom.: 1160 Cov.: 32 AF XY: 0.118 AC XY: 8797 AN XY: 74408

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0992

Gnomad4 EAS AF: 0.0957

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0995

Gnomad4 OTH AF: 0.123

Alfa AF: 0.110 Hom.: 1141

Bravo AF: 0.123

Asia WGS AF: 0.146 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.67
DANN	Benign	0.73

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: rs12945290; hg19: chr17-66378997;