ENST00000672233.1:c.77-10370A>T

Variant names:

• chr6-131568741-A-T
• rs2749935
• ENST00000672233.1:c.77-10370A>T

Variant summary

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

The ENST00000672233.1(ARG1):​c.77-10370A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,962 control chromosomes in the GnomAD database, including 23,959 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 0.52 (23959 hom., cov: 31)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854
• Publications: 7 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARG1	ENST00000672233.1	c.77-10370A>T		intron_variant	Intron 2 of 7			ENSP00000499826.1
ARG1	ENST00000672052.1	n.305-7922A>T		intron_variant	Intron 3 of 4
ARG1	ENST00000673234.1	n.77-7922A>T		intron_variant	Intron 2 of 8			ENSP00000499885.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79387 AN: 151844 Hom.: 23903 Cov.: 31

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.523 AC: 79504 AN: 151962 Hom.: 23959 Cov.: 31 AF XY: 0.520 AC XY: 38660 AN XY: 74296

African (AFR) AF: 0.841 AC: 34881 AN: 41468

American (AMR) AF: 0.508 AC: 7763 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1477 AN: 3466

East Asian (EAS) AF: 0.336 AC: 1732 AN: 5154

South Asian (SAS) AF: 0.399 AC: 1928 AN: 4828

European-Finnish (FIN) AF: 0.392 AC: 4130 AN: 10524

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26041 AN: 67940

Other (OTH) AF: 0.490 AC: 1030 AN: 2102

Alfa AF: 0.447 Hom.: 2063

Bravo AF: 0.545

Asia WGS AF: 0.381 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.66
PhyloP100		-0.85

Splicing

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

Other links and lift over

dbSNP: rs2749935; hg19: chr6-131889881;