6-131570680-A-G

Variant names:

• chr6-131570680-A-G
• rs2781659
• ENST00000672233.1:c.77-8431A>G

Variant summary

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

The ENST00000672233.1(ARG1):​c.77-8431A>G 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 152,110 control chromosomes in the GnomAD database, including 15,094 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 (15094 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 34 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 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.77-8431A>G		intron_variant	Intron 2 of 7			ENSP00000499826.1
ARG1	ENST00000672052.1	n.305-5983A>G		intron_variant	Intron 3 of 4
ARG1	ENST00000673234.1	n.77-5983A>G		intron_variant	Intron 2 of 8			ENSP00000499885.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63788 AN: 151992 Hom.: 15057 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.420 AC: 63882 AN: 152110 Hom.: 15094 Cov.: 32 AF XY: 0.421 AC XY: 31287 AN XY: 74348

African (AFR) AF: 0.645 AC: 26752 AN: 41504

American (AMR) AF: 0.428 AC: 6536 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1421 AN: 3472

East Asian (EAS) AF: 0.325 AC: 1681 AN: 5172

South Asian (SAS) AF: 0.342 AC: 1648 AN: 4820

European-Finnish (FIN) AF: 0.338 AC: 3582 AN: 10590

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21009 AN: 67978

Other (OTH) AF: 0.392 AC: 826 AN: 2106

Alfa AF: 0.363 Hom.: 18602

Bravo AF: 0.435

Asia WGS AF: 0.351 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.9
DANN	Benign	0.46
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs2781659; hg19: chr6-131891820; COSMIC: COSV51580869;