rs2608912

Positions:

• chr6-131548643-T-C
• chr6-131548643-T-G

Variant summary

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

The ENST00000672233.1(ARG1):​c.76+1445T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,062 control chromosomes in the GnomAD database, including 6,639 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 0.28 (6639 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.131548643T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARG1	ENST00000672233.1	c.76+1445T>C		intron_variant				ENSP00000499826.1
ARG1	ENST00000672052.1	n.304+1445T>C		intron_variant
ARG1	ENST00000673234.1	n.76+1445T>C		intron_variant				ENSP00000499885.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43023 AN: 151944 Hom.: 6623 Cov.: 32

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.283 AC: 43091 AN: 152062 Hom.: 6639 Cov.: 32 AF XY: 0.287 AC XY: 21362 AN XY: 74322

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.251

Alfa AF: 0.235 Hom.: 1991

Bravo AF: 0.291

Asia WGS AF: 0.282 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2608912; hg19: chr6-131869783;