rs60389358

chr6-131572417-C-T

Variant summary

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

The ENST00000672233.1(ARG1):c.77-6694C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,076 control chromosomes in the GnomAD database, including 1,007 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 0.11 (1007 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 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.77-6694C>T		intron_variant
ARG1	ENST00000673234.1	c.77-4246C>T		intron_variant, NMD_transcript_variant
ARG1	ENST00000672052.1	n.305-4246C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16813 AN: 151958 Hom.: 999 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.00810

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.111 AC: 16857 AN: 152076 Hom.: 1007 Cov.: 32 AF XY: 0.108 AC XY: 8012 AN XY: 74322

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0874

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.00812

Gnomad4 SAS AF: 0.0805

Gnomad4 FIN AF: 0.0727

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.116

Alfa AF: 0.116 Hom.: 174

Bravo AF: 0.113

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	6.4
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60389358; hg19: chr6-131893557;