6-131573218-C-T

Position:

• chr6-131573218-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000672233.1(ARG1):​c.77-5893C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,561,732 control chromosomes in the GnomAD database, including 574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (96 hom., cov: 31)
  • Exomes 𝑓: 0.022 (478 hom.)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.09

Genes affected

ARG1 (HGNC:663): (arginase 1) Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exist (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type I isoform encoded by this gene, is a cytosolic enzyme and expressed predominantly in the liver as a component of the urea cycle. Inherited deficiency of this enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 6-131573218-C-T is Benign according to our data. Variant chr6-131573218-C-T is described in ClinVar as [Benign]. Clinvar id is 355315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARG1	NM_000045.4			upstream_gene_variant		ENST00000368087.8
ARG1	NM_001244438.2			upstream_gene_variant
ARG1	NM_001369020.1			upstream_gene_variant
ARG1	NR_160934.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARG1	ENST00000368087.8			upstream_gene_variant		1	NM_000045.4	P3

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4635 AN: 151936 Hom.: 96 Cov.: 31

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.00436

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0422

GnomAD4 exome AF: 0.0215 AC: 30355 AN: 1409678 Hom.: 478 Cov.: 25 AF XY: 0.0221 AC XY: 15571 AN XY: 704316

Gnomad4 AFR exome AF: 0.0539

Gnomad4 AMR exome AF: 0.0225

Gnomad4 ASJ exome AF: 0.0463

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.0276

Gnomad4 FIN exome AF: 0.00585

Gnomad4 NFE exome AF: 0.0205

Gnomad4 OTH exome AF: 0.0258

GnomAD4 genome AF: 0.0305 AC: 4642 AN: 152054 Hom.: 96 Cov.: 31 AF XY: 0.0304 AC XY: 2258 AN XY: 74324

Gnomad4 AFR AF: 0.0525

Gnomad4 AMR AF: 0.0369

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0229

Gnomad4 FIN AF: 0.00436

Gnomad4 NFE AF: 0.0214

Gnomad4 OTH AF: 0.0418

Alfa AF: 0.0279 Hom.: 8

Bravo AF: 0.0340

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Arginase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.89

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: rs17788484; hg19: chr6-131894358;