rs4286653

Positions:

• chr5-150300696-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ARSI	NM_001012301.4	c.311+1367C>T		intron_variant		ENST00000328668.8	NP_001012301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSI	ENST00000328668.8	c.311+1367C>T		intron_variant		1	NM_001012301.4	ENSP00000333395	P1
ARSI	ENST00000509146.1	c.-118-2084C>T		intron_variant		4		ENSP00000420955
ARSI	ENST00000515301.2	c.-118-2084C>T		intron_variant		4		ENSP00000426879

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

Gnomad4 AFR AF: 0.0860

Gnomad4 AMR AF: 0.0717

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.0688

Gnomad4 SAS AF: 0.0609

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.106

Alfa AF: 0.107 Hom.: 1185

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

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: rs4286653; hg19: chr5-149680259;