6-131558665-C-T

Variant names:

• chr6-131558665-C-T
• rs3895535
• ENST00000672233.1:c.76+11467C>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+11467C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,058 control chromosomes in the GnomAD database, including 2,049 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 0.14 (2049 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 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+11467C>T		intron_variant	Intron 2 of 7			ENSP00000499826.1
ARG1	ENST00000672052.1	n.304+11467C>T		intron_variant	Intron 3 of 4
ARG1	ENST00000673234.1	n.76+11467C>T		intron_variant	Intron 2 of 8			ENSP00000499885.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21695 AN: 151944 Hom.: 2051 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.143 AC: 21701 AN: 152058 Hom.: 2049 Cov.: 32 AF XY: 0.147 AC XY: 10947 AN XY: 74304

African (AFR) AF: 0.0315 AC: 1309 AN: 41496

American (AMR) AF: 0.223 AC: 3406 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3470

East Asian (EAS) AF: 0.149 AC: 772 AN: 5168

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4814

European-Finnish (FIN) AF: 0.218 AC: 2293 AN: 10540

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11939 AN: 67986

Other (OTH) AF: 0.126 AC: 265 AN: 2108

Alfa AF: 0.160 Hom.: 6789

Bravo AF: 0.136

Asia WGS AF: 0.144 AC: 502 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	1.4
DANN	Benign	0.56
PhyloP100		-0.028

Splicing

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

Other links and lift over

dbSNP: rs3895535; hg19: chr6-131879805;