rs12645879

Variant names:

• chr4-113921586-T-C
• rs12645879
• NM_024590.4:c.399-17911A>G

Variant summary

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

The NM_024590.4(ARSJ):​c.399-17911A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,896 control chromosomes in the GnomAD database, including 24,126 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 0.56 (24126 hom., cov: 31)
• Consequence: ARSJ NM_024590.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 4 publications found

Genes affected

ARSJ (HGNC:26286): (arylsulfatase family member J) Sulfatases (EC 3.1.5.6), such as ARSJ, hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005 [PubMed 16174644]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARSJ	NM_024590.4	c.399-17911A>G		intron_variant	Intron 1 of 1	ENST00000315366.8	NP_078866.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARSJ	ENST00000315366.8	c.399-17911A>G		intron_variant	Intron 1 of 1	1	NM_024590.4	ENSP00000320219.7
ARSJ	ENST00000509829.1	n.399-14841A>G		intron_variant	Intron 2 of 3	1		ENSP00000421327.1
ARSJ	ENST00000636527.1	n.400-17911A>G		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84838 AN: 151776 Hom.: 24104 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.559 AC: 84911 AN: 151896 Hom.: 24126 Cov.: 31 AF XY: 0.567 AC XY: 42063 AN XY: 74232

African (AFR) AF: 0.511 AC: 21182 AN: 41412

American (AMR) AF: 0.592 AC: 9015 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1344 AN: 3466

East Asian (EAS) AF: 0.801 AC: 4140 AN: 5170

South Asian (SAS) AF: 0.640 AC: 3076 AN: 4810

European-Finnish (FIN) AF: 0.686 AC: 7232 AN: 10548

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37117 AN: 67938

Other (OTH) AF: 0.547 AC: 1156 AN: 2112

Alfa AF: 0.544 Hom.: 44272

Bravo AF: 0.549

Asia WGS AF: 0.724 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		-0.099
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: rs12645879; hg19: chr4-114842742;