rs2608937

chr6-131567007-G-Achr6-131567007-G-C

Variant summary

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

The ENST00000672233.1(ARG1):c.77-12104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,150 control chromosomes in the GnomAD database, including 2,087 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 0.15 (2087 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARG1	ENST00000672233.1	c.77-12104G>A		intron_variant
ARG1	ENST00000673234.1	c.77-9656G>A		intron_variant, NMD_transcript_variant
ARG1	ENST00000672052.1	n.305-9656G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22408 AN: 152032 Hom.: 2089 Cov.: 32

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.128

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.147 AC: 22420 AN: 152150 Hom.: 2087 Cov.: 32 AF XY: 0.152 AC XY: 11306 AN XY: 74370

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.127

Alfa AF: 0.168 Hom.: 2113

Bravo AF: 0.142

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.6
Dann	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2608937; hg19: chr6-131888147;