rs4286653

Variant names:

• chr5-150300696-G-A
• rs4286653
• NM_001012301.4:c.311+1367C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001012301.4(ARSI):​c.311+1367C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 152,280 control chromosomes in the GnomAD database, including 751 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 0.098 (751 hom., cov: 33)
• Consequence: ARSI NM_001012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSI	NM_001012301.4	c.311+1367C>T		intron_variant	Intron 1 of 1	ENST00000328668.8	NP_001012301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSI	ENST00000328668.8	c.311+1367C>T		intron_variant	Intron 1 of 1	1	NM_001012301.4	ENSP00000333395.7
ARSI	ENST00000515301.2	c.-118-2084C>T		intron_variant	Intron 1 of 1	4		ENSP00000426879.2
ARSI	ENST00000509146.1	c.-118-2084C>T		intron_variant	Intron 1 of 1	4		ENSP00000420955.1

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14842 AN: 152162 Hom.: 750 Cov.: 33

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.0606

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0975 AC: 14854 AN: 152280 Hom.: 751 Cov.: 33 AF XY: 0.0966 AC XY: 7193 AN XY: 74460

African (AFR) AF: 0.0860 AC: 3573 AN: 41564

American (AMR) AF: 0.0717 AC: 1098 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3470

East Asian (EAS) AF: 0.0688 AC: 357 AN: 5188

South Asian (SAS) AF: 0.0609 AC: 294 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1397 AN: 10604

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7556 AN: 68002

Other (OTH) AF: 0.106 AC: 225 AN: 2114

Alfa AF: 0.106 Hom.: 1407

Bravo AF: 0.0928

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		1.3
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: rs4286653; hg19: chr5-149680259;