rs7140310

Positions:

• chr14-67644020-T-G

Variant summary

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

The NM_001172.4(ARG2):​c.363-1623T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,138 control chromosomes in the GnomAD database, including 2,281 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 0.17 (2281 hom., cov: 32)
• Consequence: ARG2 NM_001172.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARG2	NM_001172.4	c.363-1623T>G		intron_variant		ENST00000261783.4	NP_001163.1
GPHN	XM_047430879.1	c.1313-91175T>G		intron_variant			XP_047286835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARG2	ENST00000261783.4	c.363-1623T>G		intron_variant		1	NM_001172.4	ENSP00000261783	P1
ARG2	ENST00000556491.1	n.360+1657T>G		intron_variant, non_coding_transcript_variant		5
ARG2	ENST00000557120.5	n.405-1623T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25801 AN: 152020 Hom.: 2274 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.170 AC: 25838 AN: 152138 Hom.: 2281 Cov.: 32 AF XY: 0.168 AC XY: 12526 AN XY: 74394

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.177

Alfa AF: 0.145 Hom.: 1660

Bravo AF: 0.176

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.36
DANN	Benign	0.34

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: rs7140310; hg19: chr14-68110737;