6-131573218-C-T

Variant names:

• chr6-131573218-C-T
• rs17788484
• ENST00000875750.1:c.-65C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000875750.1(ARG1):​c.-65C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,561,732 control chromosomes in the GnomAD database, including 574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (96 hom., cov: 31)
  • Exomes 𝑓: 0.022 (478 hom.)
• Consequence: ARG1 ENST00000875750.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.09
• Publications: 8 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 6-131573218-C-T is Benign according to our data. Variant chr6-131573218-C-T is described in ClinVar as Benign. ClinVar VariationId is 355315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000875750.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARG1	NM_000045.4	MANE Select	c.-65C>T		upstream_gene	N/A	NP_000036.2
	ARG1	NM_001244438.2		c.-65C>T		upstream_gene	N/A	NP_001231367.1	P05089-2
	ARG1	NM_001369020.1		c.-65C>T		upstream_gene	N/A	NP_001355949.1	A0A5F9ZH78

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARG1	ENST00000875750.1		c.-65C>T		5_prime_UTR	Exon 1 of 7	ENSP00000545809.1
	ARG1	ENST00000672233.1		c.77-5893C>T		intron	N/A	ENSP00000499826.1	A0A5F9ZGN6
	ARG1	ENST00000469293.1	TSL:3	n.25C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4635 AN: 151936 Hom.: 96 Cov.: 31

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.00436

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0422

GnomAD4 exome AF: 0.0215 AC: 30355 AN: 1409678 Hom.: 478 Cov.: 25 AF XY: 0.0221 AC XY: 15571 AN XY: 704316

African (AFR) AF: 0.0539 AC: 1743 AN: 32332

American (AMR) AF: 0.0225 AC: 1003 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.0463 AC: 1194 AN: 25806

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39444

South Asian (SAS) AF: 0.0276 AC: 2347 AN: 85160

European-Finnish (FIN) AF: 0.00585 AC: 312 AN: 53344

Middle Eastern (MID) AF: 0.0716 AC: 406 AN: 5674

European-Non Finnish (NFE) AF: 0.0205 AC: 21829 AN: 1064764

Other (OTH) AF: 0.0258 AC: 1515 AN: 58616

GnomAD4 genome AF: 0.0305 AC: 4642 AN: 152054 Hom.: 96 Cov.: 31 AF XY: 0.0304 AC XY: 2258 AN XY: 74324

African (AFR) AF: 0.0525 AC: 2177 AN: 41474

American (AMR) AF: 0.0369 AC: 564 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0229 AC: 110 AN: 4812

European-Finnish (FIN) AF: 0.00436 AC: 46 AN: 10560

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0214 AC: 1457 AN: 67984

Other (OTH) AF: 0.0418 AC: 88 AN: 2106

Alfa AF: 0.0279 Hom.: 8

Bravo AF: 0.0340

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Arginase deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.89
PhyloP100		1.1
PromoterAI		-0.013	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs17788484; hg19: chr6-131894358;