6-131557035-T-C

Variant names:

• chr6-131557035-T-C
• rs2608976
• ENST00000672233.1:c.76+9837T>C

Variant summary

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

The ENST00000672233.1(ARG1):​c.76+9837T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,962 control chromosomes in the GnomAD database, including 6,803 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 0.29 (6803 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.388 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.76+9837T>C		intron_variant	Intron 2 of 7			ENSP00000499826.1
ARG1	ENST00000672052.1	n.304+9837T>C		intron_variant	Intron 3 of 4
ARG1	ENST00000673234.1	n.76+9837T>C		intron_variant	Intron 2 of 8			ENSP00000499885.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43650 AN: 151842 Hom.: 6782 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.288 AC: 43726 AN: 151962 Hom.: 6803 Cov.: 32 AF XY: 0.292 AC XY: 21688 AN XY: 74266

African (AFR) AF: 0.393 AC: 16283 AN: 41462

American (AMR) AF: 0.338 AC: 5161 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3464

East Asian (EAS) AF: 0.314 AC: 1620 AN: 5162

South Asian (SAS) AF: 0.262 AC: 1261 AN: 4812

European-Finnish (FIN) AF: 0.298 AC: 3133 AN: 10520

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14832 AN: 67954

Other (OTH) AF: 0.255 AC: 538 AN: 2110

Alfa AF: 0.248 Hom.: 638

Bravo AF: 0.295

Asia WGS AF: 0.286 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.74
PhyloP100		-0.94

Splicing

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

Other links and lift over

dbSNP: rs2608976; hg19: chr6-131878175;