5-150298733-A-G

Position:

• chr5-150298733-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.312-121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 851,110 control chromosomes in the GnomAD database, including 238,817 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 0.68 (36384 hom., cov: 32)
  • Exomes 𝑓: 0.76 (202433 hom.)
• Consequence: ARSI NM_001012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARSI	NM_001012301.4	c.312-121T>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.312-121T>C		intron_variant		1	NM_001012301.4	ENSP00000333395.7
ARSI	ENST00000515301.2	c.-118-121T>C		intron_variant		4		ENSP00000426879.2
ARSI	ENST00000509146.1	c.-118-121T>C		intron_variant		4		ENSP00000420955.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104031 AN: 151976 Hom.: 36379 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.672

GnomAD4 exome AF: 0.758 AC: 530018 AN: 699014 Hom.: 202433 AF XY: 0.759 AC XY: 269182 AN XY: 354884

Gnomad4 AFR exome AF: 0.531

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.748

Gnomad4 EAS exome AF: 0.742

Gnomad4 SAS exome AF: 0.745

Gnomad4 FIN exome AF: 0.764

Gnomad4 NFE exome AF: 0.777

Gnomad4 OTH exome AF: 0.730

GnomAD4 genome AF: 0.684 AC: 104063 AN: 152096 Hom.: 36384 Cov.: 32 AF XY: 0.683 AC XY: 50797 AN XY: 74354

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.673

Alfa AF: 0.708 Hom.: 5666

Bravo AF: 0.667

Asia WGS AF: 0.703 AC: 2443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.49

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: rs6579785; hg19: chr5-149678296;