rs6579786

Positions:

• chr5-150298762-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012301.4(ARSI):​c.312-150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 668,200 control chromosomes in the GnomAD database, including 274,686 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 0.89 (59906 hom., cov: 32)
  • Exomes 𝑓: 0.91 (214780 hom.)
• Consequence: ARSI NM_001012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSI	NM_001012301.4	c.312-150T>C		intron_variant		ENST00000328668.8	NP_001012301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARSI	ENST00000328668.8	c.312-150T>C		intron_variant		1	NM_001012301.4	ENSP00000333395	P1
ARSI	ENST00000509146.1	c.-118-150T>C		intron_variant		4		ENSP00000420955
ARSI	ENST00000515301.2	c.-118-150T>C		intron_variant		4		ENSP00000426879

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134657 AN: 152096 Hom.: 59856 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.874

GnomAD4 exome AF: 0.911 AC: 470130 AN: 515984 Hom.: 214780 AF XY: 0.910 AC XY: 243639 AN XY: 267736

Gnomad4 AFR exome AF: 0.832

Gnomad4 AMR exome AF: 0.743

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.876

Gnomad4 FIN exome AF: 0.954

Gnomad4 NFE exome AF: 0.930

Gnomad4 OTH exome AF: 0.902

GnomAD4 genome AF: 0.885 AC: 134762 AN: 152216 Hom.: 59906 Cov.: 32 AF XY: 0.884 AC XY: 65818 AN XY: 74452

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.957

Gnomad4 NFE AF: 0.929

Gnomad4 OTH AF: 0.875

Alfa AF: 0.898 Hom.: 7661

Bravo AF: 0.868

Asia WGS AF: 0.877 AC: 3049 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	4.2
DANN	Benign	0.66

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: rs6579786; hg19: chr5-149678325;