6-131552595-C-T

Variant names:

• chr6-131552595-C-T
• rs2608921
• ENST00000672233.1:c.76+5397C>T

Variant summary

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

The ENST00000672233.1(ARG1):​c.76+5397C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,410 control chromosomes in the GnomAD database, including 9,092 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 0.32 (9092 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• 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: 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 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+5397C>T		intron_variant	Intron 2 of 7			ENSP00000499826.1
ARG1	ENST00000672052.1	n.304+5397C>T		intron_variant	Intron 3 of 4
ARG1	ENST00000673234.1	n.76+5397C>T		intron_variant	Intron 2 of 8			ENSP00000499885.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48828 AN: 151296 Hom.: 9076 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.323 AC: 48896 AN: 151410 Hom.: 9092 Cov.: 32 AF XY: 0.326 AC XY: 24101 AN XY: 73902

African (AFR) AF: 0.514 AC: 21231 AN: 41342

American (AMR) AF: 0.350 AC: 5325 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3464

East Asian (EAS) AF: 0.314 AC: 1618 AN: 5150

South Asian (SAS) AF: 0.262 AC: 1259 AN: 4814

European-Finnish (FIN) AF: 0.300 AC: 3106 AN: 10350

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14838 AN: 67784

Other (OTH) AF: 0.287 AC: 602 AN: 2098

Alfa AF: 0.184 Hom.: 720

Bravo AF: 0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.26
PhyloP100		-0.54

Splicing

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

Other links and lift over

dbSNP: rs2608921; hg19: chr6-131873735; COSMIC: COSV69631147;