chr4-113921969-C-T

Variant names:

• chr4-113921969-C-T
• rs4441820
• NM_024590.4:c.399-18294G>A

Variant summary

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

The NM_024590.4(ARSJ):​c.399-18294G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,940 control chromosomes in the GnomAD database, including 24,067 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 (24067 hom., cov: 32)
• Consequence: ARSJ NM_024590.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 1 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024590.4. 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
	ARSJ	NM_024590.4	MANE Select	c.399-18294G>A		intron	N/A	NP_078866.3
	ARSJ	NM_001354210.2		c.399-18294G>A		intron	N/A	NP_001341139.1
	ARSJ	NM_001354211.2		c.1-15224G>A		intron	N/A	NP_001341140.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARSJ	ENST00000315366.8	TSL:1 MANE Select	c.399-18294G>A		intron	N/A	ENSP00000320219.7
	ARSJ	ENST00000509829.1	TSL:1	n.399-15224G>A		intron	N/A	ENSP00000421327.1
	ARSJ	ENST00000636527.1	TSL:5	n.400-18294G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84764 AN: 151824 Hom.: 24044 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.490

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: 0.558 AC: 84839 AN: 151940 Hom.: 24067 Cov.: 32 AF XY: 0.566 AC XY: 42040 AN XY: 74278

African (AFR) AF: 0.509 AC: 21101 AN: 41422

American (AMR) AF: 0.592 AC: 9026 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3464

East Asian (EAS) AF: 0.800 AC: 4136 AN: 5168

South Asian (SAS) AF: 0.638 AC: 3075 AN: 4820

European-Finnish (FIN) AF: 0.685 AC: 7243 AN: 10570

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.546 AC: 37107 AN: 67930

Other (OTH) AF: 0.548 AC: 1158 AN: 2114

Alfa AF: 0.547 Hom.: 3462

Bravo AF: 0.548

Asia WGS AF: 0.723 AC: 2515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.19
PhyloP100		-0.096
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: rs4441820; hg19: chr4-114843125;