chr6-131555157-T-G

Variant names:

• chr6-131555157-T-G
• rs2608981
• ENST00000672233.1:c.76+7959T>G

Variant summary

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

The ENST00000672233.1(ARG1):​c.76+7959T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,876 control chromosomes in the GnomAD database, including 6,761 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 (6761 hom., cov: 32)
• Consequence: ARG1 ENST00000672233.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.800
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 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+7959T>G		intron_variant	Intron 2 of 7			ENSP00000499826.1
ARG1	ENST00000672052.1	n.304+7959T>G		intron_variant	Intron 3 of 4
ARG1	ENST00000673234.1	n.76+7959T>G		intron_variant	Intron 2 of 8			ENSP00000499885.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43498 AN: 151760 Hom.: 6740 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.287 AC: 43573 AN: 151876 Hom.: 6761 Cov.: 32 AF XY: 0.291 AC XY: 21608 AN XY: 74244

African (AFR) AF: 0.392 AC: 16234 AN: 41410

American (AMR) AF: 0.335 AC: 5108 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1620 AN: 5182

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

European-Finnish (FIN) AF: 0.296 AC: 3113 AN: 10500

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14811 AN: 67940

Other (OTH) AF: 0.254 AC: 535 AN: 2110

Alfa AF: 0.257 Hom.: 688

Bravo AF: 0.294

Asia WGS AF: 0.286 AC: 989 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.70
PhyloP100		0.80

Splicing

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

Other links and lift over

dbSNP: rs2608981; hg19: chr6-131876297;