rs60389358

Variant names:

• chr6-131572417-C-T
• rs60389358
• ENST00000672233.1:c.77-6694C>T

Variant summary

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

The ENST00000672233.1(ARG1):​c.77-6694C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,076 control chromosomes in the GnomAD database, including 1,007 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 0.11 (1007 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000672233.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARG1	ENST00000672233.1		c.77-6694C>T		intron	N/A	ENSP00000499826.1
	ARG1	ENST00000672052.1		n.305-4246C>T		intron	N/A
	ARG1	ENST00000673234.1		n.77-4246C>T		intron	N/A	ENSP00000499885.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16813 AN: 151958 Hom.: 999 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0527

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.00810

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.111 AC: 16857 AN: 152076 Hom.: 1007 Cov.: 32 AF XY: 0.108 AC XY: 8012 AN XY: 74322

African (AFR) AF: 0.123 AC: 5124 AN: 41502

American (AMR) AF: 0.0874 AC: 1335 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3470

East Asian (EAS) AF: 0.00812 AC: 42 AN: 5172

South Asian (SAS) AF: 0.0805 AC: 388 AN: 4818

European-Finnish (FIN) AF: 0.0727 AC: 767 AN: 10556

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8065 AN: 67968

Other (OTH) AF: 0.116 AC: 244 AN: 2112

Alfa AF: 0.116 Hom.: 1656

Bravo AF: 0.113

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.4
DANN	Benign	0.78
PhyloP100		-0.81

Splicing

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

Other links and lift over

dbSNP: rs60389358; hg19: chr6-131893557;