rs2781665

Variant names:

• chr6-131572107-A-T
• rs2781665
• ENST00000672233.1:c.77-7004A>T

Variant summary

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

The ENST00000672233.1(ARG1):​c.77-7004A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 151,980 control chromosomes in the GnomAD database, including 13,103 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 0.40 (13103 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 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.77-7004A>T		intron_variant	Intron 2 of 7			ENSP00000499826.1
ARG1	ENST00000672052.1	n.305-4556A>T		intron_variant	Intron 3 of 4
ARG1	ENST00000673234.1	n.77-4556A>T		intron_variant	Intron 2 of 8			ENSP00000499885.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60439 AN: 151862 Hom.: 13076 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.398 AC: 60517 AN: 151980 Hom.: 13103 Cov.: 32 AF XY: 0.400 AC XY: 29730 AN XY: 74274

African (AFR) AF: 0.572 AC: 23700 AN: 41424

American (AMR) AF: 0.414 AC: 6327 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3464

East Asian (EAS) AF: 0.326 AC: 1684 AN: 5172

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4820

European-Finnish (FIN) AF: 0.339 AC: 3580 AN: 10556

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20943 AN: 67960

Other (OTH) AF: 0.376 AC: 794 AN: 2110

Alfa AF: 0.358 Hom.: 1273

Bravo AF: 0.410

Asia WGS AF: 0.341 AC: 1189 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.84
PhyloP100		-0.098

Splicing

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

Other links and lift over

dbSNP: rs2781665; hg19: chr6-131893247; COSMIC: COSV51581727;