rs2608937

Variant names:

• chr6-131567007-G-A
• rs2608937
• ENST00000672233.1:c.77-12104G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-131567007-G-A
• chr6-131567007-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 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.77-12104G>A		intron	N/A	ENSP00000499826.1
	ARG1	ENST00000672052.1		n.305-9656G>A		intron	N/A
	ARG1	ENST00000673234.1		n.77-9656G>A		intron	N/A	ENSP00000499885.1

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

African (AFR) AF: 0.0490 AC: 2033 AN: 41530

American (AMR) AF: 0.223 AC: 3414 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3470

East Asian (EAS) AF: 0.148 AC: 766 AN: 5176

South Asian (SAS) AF: 0.217 AC: 1046 AN: 4820

European-Finnish (FIN) AF: 0.218 AC: 2300 AN: 10556

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11898 AN: 67992

Other (OTH) AF: 0.127 AC: 268 AN: 2112

Alfa AF: 0.162 Hom.: 2720

Bravo AF: 0.142

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.76
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs2608937; hg19: chr6-131888147;