rs11750343

Variant names:

• chr5-150328215-A-G
• rs11750343
• ENST00000515301.2:c.-119+11063T>C

Variant summary

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

The ENST00000515301.2(ARSI):​c.-119+11063T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,304 control chromosomes in the GnomAD database, including 712 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 0.094 (712 hom., cov: 32)
• Consequence: ARSI ENST00000515301.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 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.-119+11063T>C		intron_variant	Intron 1 of 1	4		ENSP00000426879.2
ARSI	ENST00000509146.1	c.-119+10985T>C		intron_variant	Intron 1 of 1	4		ENSP00000420955.1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14275 AN: 152186 Hom.: 714 Cov.: 32

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0563

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0900

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.0937 AC: 14272 AN: 152304 Hom.: 712 Cov.: 32 AF XY: 0.0941 AC XY: 7005 AN XY: 74476

African (AFR) AF: 0.0989 AC: 4110 AN: 41558

American (AMR) AF: 0.0552 AC: 844 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0563 AC: 195 AN: 3466

East Asian (EAS) AF: 0.221 AC: 1148 AN: 5188

South Asian (SAS) AF: 0.0805 AC: 389 AN: 4830

European-Finnish (FIN) AF: 0.0900 AC: 955 AN: 10616

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0930 AC: 6328 AN: 68024

Other (OTH) AF: 0.0899 AC: 190 AN: 2114

Alfa AF: 0.0905 Hom.: 934

Bravo AF: 0.0926

Asia WGS AF: 0.136 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.79
PhyloP100		-1.1
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: rs11750343; hg19: chr5-149707778;