ENST00000672233.1:c.77-7904T>A

Variant names:

• chr6-131571207-T-A
• rs2781663
• ENST00000672233.1:c.77-7904T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 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.77-7904T>A		intron	N/A	ENSP00000499826.1	A0A5F9ZGN6
	ARG1	ENST00000672052.1		n.305-5456T>A		intron	N/A
	ARG1	ENST00000673234.1		n.77-5456T>A		intron	N/A	ENSP00000499885.1	A0A5F9ZGY6

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

African (AFR) AF: 0.645 AC: 26738 AN: 41444

American (AMR) AF: 0.428 AC: 6543 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1421 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1679 AN: 5160

South Asian (SAS) AF: 0.342 AC: 1650 AN: 4820

European-Finnish (FIN) AF: 0.339 AC: 3587 AN: 10568

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 21005 AN: 67962

Other (OTH) AF: 0.393 AC: 829 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.82
DANN	Benign	0.79
PhyloP100		-0.31

Splicing

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

Other links and lift over

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