17-68386068-T-C

Variant names:

• chr17-68386068-T-C
• rs11655081
• NM_001267727.2:c.1091+896T>C

Variant summary

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

The NM_001267727.2(ARSG):​c.1091+896T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,178 control chromosomes in the GnomAD database, including 5,239 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 0.18 (5239 hom., cov: 31)
• Consequence: ARSG NM_001267727.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.748
• Publications: 18 publications found

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]

ARSG Gene-Disease associations (from GenCC):

• Usher syndrome, type 4

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Usher syndrome type 3

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSG	NM_001267727.2	c.1091+896T>C		intron_variant	Intron 9 of 11	ENST00000621439.5	NP_001254656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSG	ENST00000621439.5	c.1091+896T>C		intron_variant	Intron 9 of 11	5	NM_001267727.2	ENSP00000480910.1
ARSG	ENST00000448504.6	c.1091+896T>C		intron_variant	Intron 9 of 11	1		ENSP00000407193.2
ARSG	ENST00000452479.6	c.599+896T>C		intron_variant	Intron 8 of 10	5		ENSP00000413953.2
ARSG	ENST00000582154.5	n.849+896T>C		intron_variant	Intron 7 of 9	2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27969 AN: 152060 Hom.: 5223 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0964

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0466

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.184 AC: 28026 AN: 152178 Hom.: 5239 Cov.: 31 AF XY: 0.187 AC XY: 13884 AN XY: 74424

African (AFR) AF: 0.448 AC: 18585 AN: 41482

American (AMR) AF: 0.0962 AC: 1472 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2401 AN: 5166

South Asian (SAS) AF: 0.259 AC: 1247 AN: 4812

European-Finnish (FIN) AF: 0.0273 AC: 290 AN: 10630

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.0466 AC: 3169 AN: 67998

Other (OTH) AF: 0.166 AC: 351 AN: 2112

Alfa AF: 0.117 Hom.: 4388

Bravo AF: 0.200

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	12
DANN	Benign	0.50
PhyloP100		0.75
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: rs11655081; hg19: chr17-66382209;