rs13184396

Variant names:

• chr5-150309610-C-T
• rs13184396
• ENST00000515301.2:c.-118-10998G>A

Variant summary

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

The ENST00000515301.2(ARSI):​c.-118-10998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,180 control chromosomes in the GnomAD database, including 2,469 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 0.16 (2469 hom., cov: 32)
• Consequence: ARSI ENST00000515301.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 4 publications found

Genes affected

ARSI (HGNC:32521): (arylsulfatase family member I) This gene encodes a protein that belongs to a large family of sulfatases that hydrolyze sulfate esters and sulfamates. Members of this family play a role in several cellular processes, including hormone synthesis, cell signaling in development and degradation of macromolecules. The protein encoded by this gene is thought to be secreted, and to function in extracellular space. [provided by RefSeq, Jul 2016]

ARSI Gene-Disease associations (from GenCC):

• autosomal recessive spastic paraplegia type 66

  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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSI	ENST00000515301.2	c.-118-10998G>A		intron_variant	Intron 1 of 1	4		ENSP00000426879.2
ARSI	ENST00000509146.1	c.-118-10998G>A		intron_variant	Intron 1 of 1	4		ENSP00000420955.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23890 AN: 152062 Hom.: 2468 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.157 AC: 23890 AN: 152180 Hom.: 2469 Cov.: 32 AF XY: 0.153 AC XY: 11374 AN XY: 74408

African (AFR) AF: 0.0404 AC: 1677 AN: 41540

American (AMR) AF: 0.145 AC: 2210 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0817 AC: 393 AN: 4812

European-Finnish (FIN) AF: 0.233 AC: 2467 AN: 10594

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15475 AN: 67968

Other (OTH) AF: 0.165 AC: 349 AN: 2110

Alfa AF: 0.202 Hom.: 6233

Bravo AF: 0.148

Asia WGS AF: 0.0420 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.9
DANN	Benign	0.61
PhyloP100		-0.096
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13184396; hg19: chr5-149689173;