6-131572419-G-T

Variant names:

• chr6-131572419-G-T
• rs2781666
• ENST00000672233.1:c.77-6692G>T

Variant summary

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

The ENST00000672233.1(ARG1):​c.77-6692G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,842 control chromosomes in the GnomAD database, including 17,015 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 0.44 (17015 hom., cov: 31)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 30 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Myriad Women’s Health

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARG1	ENST00000672233.1		c.77-6692G>T		intron	N/A	ENSP00000499826.1	A0A5F9ZGN6
	ARG1	ENST00000672052.1		n.305-4244G>T		intron	N/A
	ARG1	ENST00000673234.1		n.77-4244G>T		intron	N/A	ENSP00000499885.1	A0A5F9ZGY6

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66628 AN: 151724 Hom.: 16970 Cov.: 31

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.439 AC: 66732 AN: 151842 Hom.: 17015 Cov.: 31 AF XY: 0.440 AC XY: 32619 AN XY: 74208

African (AFR) AF: 0.714 AC: 29548 AN: 41406

American (AMR) AF: 0.434 AC: 6612 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1420 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1678 AN: 5156

South Asian (SAS) AF: 0.342 AC: 1648 AN: 4814

European-Finnish (FIN) AF: 0.339 AC: 3568 AN: 10512

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20974 AN: 67922

Other (OTH) AF: 0.406 AC: 855 AN: 2108

Alfa AF: 0.398 Hom.: 1823

Bravo AF: 0.458

Asia WGS AF: 0.353 AC: 1229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.39
PhyloP100		-0.032

Splicing

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

Other links and lift over

dbSNP: rs2781666; hg19: chr6-131893559;