rs2807278

Variant names:

• chr6-131488780-T-C
• rs2807278
• ENST00000672233.1:c.-43+17831T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000672233.1(ARG1):​c.-43+17831T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,054 control chromosomes in the GnomAD database, including 7,676 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 0.31 (7676 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• arginase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000672233.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARG1	ENST00000672233.1		c.-43+17831T>C		intron	N/A	ENSP00000499826.1
	ARG1	ENST00000672052.1		n.118+17831T>C		intron	N/A
	ARG1	ENST00000673234.1		n.-43+17831T>C		intron	N/A	ENSP00000499885.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47207 AN: 151936 Hom.: 7665 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.311 AC: 47250 AN: 152054 Hom.: 7676 Cov.: 32 AF XY: 0.311 AC XY: 23114 AN XY: 74324

African (AFR) AF: 0.379 AC: 15694 AN: 41432

American (AMR) AF: 0.356 AC: 5443 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 907 AN: 3468

East Asian (EAS) AF: 0.150 AC: 775 AN: 5174

South Asian (SAS) AF: 0.284 AC: 1370 AN: 4822

European-Finnish (FIN) AF: 0.291 AC: 3075 AN: 10574

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18825 AN: 67980

Other (OTH) AF: 0.296 AC: 624 AN: 2110

Alfa AF: 0.282 Hom.: 27862

Bravo AF: 0.319

Asia WGS AF: 0.199 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.78
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs2807278; hg19: chr6-131809920;