5-150306292-A-T

Variant names:

• chr5-150306292-A-T
• rs1465689
• ENST00000515301.2:c.-118-7680T>A

Variant summary

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

The ENST00000515301.2(ARSI):​c.-118-7680T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,136 control chromosomes in the GnomAD database, including 23,208 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 0.55 (23208 hom., cov: 33)
• Consequence: ARSI ENST00000515301.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000515301.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSI	ENST00000515301.2	TSL:4	c.-118-7680T>A		intron	N/A	ENSP00000426879.2
	ARSI	ENST00000509146.1	TSL:4	c.-118-7680T>A		intron	N/A	ENSP00000420955.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82875 AN: 152018 Hom.: 23158 Cov.: 33

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.545 AC: 82984 AN: 152136 Hom.: 23208 Cov.: 33 AF XY: 0.536 AC XY: 39837 AN XY: 74374

African (AFR) AF: 0.662 AC: 27487 AN: 41500

American (AMR) AF: 0.458 AC: 7003 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1756 AN: 3472

East Asian (EAS) AF: 0.369 AC: 1906 AN: 5170

South Asian (SAS) AF: 0.528 AC: 2547 AN: 4828

European-Finnish (FIN) AF: 0.400 AC: 4225 AN: 10572

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36391 AN: 67984

Other (OTH) AF: 0.523 AC: 1105 AN: 2114

Alfa AF: 0.549 Hom.: 2891

Bravo AF: 0.550

Asia WGS AF: 0.518 AC: 1800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.47
PhyloP100		-0.13
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: rs1465689; hg19: chr5-149685855; COSMIC: COSV107408799; COSMIC: COSV107408799;