Variant 6-131573218-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.09

Variant links:

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]

ARG1 links:

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ACMG classification

Classification made for transcript

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	Effect	MANE
ARG1	NM_000045.4 linkuse as main transcript	upstream_gene_variant	ENST00000368087.8
ARG1	NM_001244438.2 linkuse as main transcript	upstream_gene_variant
ARG1	NM_001369020.1 linkuse as main transcript	upstream_gene_variant
ARG1	NR_160934.1 linkuse as main transcript	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARG1	ENST00000368087.8 linkuse as main transcript			upstream_gene_variant		1	NM_000045.4	P3	P05089-1

Frequencies

GnomAD3 genomes

AF:

0.0305

AC:

4635

AN:

151936

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0221

AC XY:

15571

AN XY:

704316

show subpopulations

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.:

Cov.:

AF XY:

0.0304

AC XY:

2258

AN XY:

74324

show subpopulations

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.:

Bravo

AF:

0.0340

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over