4-113941996-C-T

Variant names:

• chr4-113941996-C-T
• rs10034059
• NM_024590.4:c.398+36441G>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.398+36441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,594 control chromosomes in the GnomAD database, including 10,774 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 0.36 (10774 hom., cov: 31)
• Consequence: ARSJ NM_024590.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 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.398+36441G>A		intron	N/A	NP_078866.3
	ARSJ	NM_001354210.2		c.398+36441G>A		intron	N/A	NP_001341139.1
	ARSJ	NM_001354211.2		c.-1+28479G>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.398+36441G>A		intron	N/A	ENSP00000320219.7
	ARSJ	ENST00000509829.1	TSL:1	n.399-35251G>A		intron	N/A	ENSP00000421327.1
	ARSJ	ENST00000636527.1	TSL:5	n.399+28479G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54861 AN: 151476 Hom.: 10740 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.363 AC: 54962 AN: 151594 Hom.: 10774 Cov.: 31 AF XY: 0.367 AC XY: 27159 AN XY: 74060

African (AFR) AF: 0.512 AC: 21160 AN: 41342

American (AMR) AF: 0.384 AC: 5823 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3464

East Asian (EAS) AF: 0.468 AC: 2390 AN: 5106

South Asian (SAS) AF: 0.363 AC: 1744 AN: 4810

European-Finnish (FIN) AF: 0.351 AC: 3694 AN: 10532

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18265 AN: 67846

Other (OTH) AF: 0.357 AC: 751 AN: 2106

Alfa AF: 0.298 Hom.: 5690

Bravo AF: 0.368

Asia WGS AF: 0.453 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.10
DANN	Benign	0.52
PhyloP100		-1.8
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: rs10034059; hg19: chr4-114863152;