rs2781663

Positions:

• chr6-131571207-T-A
• chr6-131571207-T-C
• chr6-131571207-T-G

Variant summary

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

The ENST00000672233.1(ARG1):​c.77-7904T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,004 control chromosomes in the GnomAD database, including 15,104 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 0.42 (15104 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARG1	ENST00000672233.1	c.77-7904T>A		intron_variant				ENSP00000499826
ARG1	ENST00000673234.1	c.77-5456T>A		intron_variant, NMD_transcript_variant				ENSP00000499885
ARG1	ENST00000672052.1	n.305-5456T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63785 AN: 151886 Hom.: 15066 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.420 AC: 63879 AN: 152004 Hom.: 15104 Cov.: 32 AF XY: 0.421 AC XY: 31303 AN XY: 74302

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.393

Alfa AF: 0.195 Hom.: 358

Bravo AF: 0.435

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.82
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2781663; hg19: chr6-131892347; COSMIC: COSV51581715;