rs12645879

Positions:

• chr4-113921586-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ARSJ	NM_024590.4	c.399-17911A>G		intron_variant		ENST00000315366.8	NP_078866.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSJ	ENST00000315366.8	c.399-17911A>G		intron_variant		1	NM_024590.4	ENSP00000320219	P1
ARSJ	ENST00000509829.1	c.399-14841A>G		intron_variant, NMD_transcript_variant		1		ENSP00000421327
ARSJ	ENST00000636527.1	n.400-17911A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.547

Alfa AF: 0.547 Hom.: 31092

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12645879; hg19: chr4-114842742;