rs742869

Positions:

• chr14-67646576-G-A
• chr14-67646576-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172.4(ARG2):​c.523-68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,278,946 control chromosomes in the GnomAD database, including 202,436 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 0.45 (17871 hom., cov: 32)
  • Exomes 𝑓: 0.56 (184565 hom.)
• Consequence: ARG2 NM_001172.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

Genes affected

ARG2 (HGNC:664): (arginase 2) Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exists (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type II isoform encoded by this gene, is located in the mitochondria and expressed in extra-hepatic tissues, especially kidney. The physiologic role of this isoform is poorly understood; it is thought to play a role in nitric oxide and polyamine metabolism. Transcript variants of the type II gene resulting from the use of alternative polyadenylation sites have been described. [provided by RefSeq, Jul 2008]

GPHN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARG2	NM_001172.4	c.523-68G>A		intron_variant		ENST00000261783.4	NP_001163.1
GPHN	XM_047430879.1	c.1313-88619G>A		intron_variant			XP_047286835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARG2	ENST00000261783.4	c.523-68G>A		intron_variant		1	NM_001172.4	ENSP00000261783	P1
ARG2	ENST00000557319.1	n.129G>A		non_coding_transcript_exon_variant	1/4	2
ARG2	ENST00000556491.1	n.361-68G>A		intron_variant, non_coding_transcript_variant		5
ARG2	ENST00000557120.5	n.565-68G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68165 AN: 151952 Hom.: 17875 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.560 AC: 630619 AN: 1126876 Hom.: 184565 Cov.: 15 AF XY: 0.556 AC XY: 317790 AN XY: 571476

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.448 AC: 68171 AN: 152070 Hom.: 17871 Cov.: 32 AF XY: 0.444 AC XY: 32988 AN XY: 74338

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.421

Alfa AF: 0.560 Hom.: 32156

Bravo AF: 0.423

Asia WGS AF: 0.310 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs742869; hg19: chr14-68113293; COSMIC: COSV53619850; COSMIC: COSV53619850;