chr14-67627548-G-C

Position:

• chr14-67627548-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.184+6582G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,900 control chromosomes in the GnomAD database, including 3,975 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 0.21 (3975 hom., cov: 31)
• Consequence: ARG2 NM_001172.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.683

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARG2	NM_001172.4	c.184+6582G>C		intron_variant		ENST00000261783.4
LOC124903331	XR_007064218.1	n.2914C>G		non_coding_transcript_exon_variant	2/2
GPHN	XM_047430879.1	c.1313-107647G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARG2	ENST00000261783.4	c.184+6582G>C		intron_variant		1	NM_001172.4	P1
	ENST00000662787.1	n.2876C>G		non_coding_transcript_exon_variant	2/2
ARG2	ENST00000556491.1	n.182+6582G>C		intron_variant, non_coding_transcript_variant		5
ARG2	ENST00000557120.5	n.226+6582G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31108 AN: 151782 Hom.: 3955 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.205 AC: 31178 AN: 151900 Hom.: 3975 Cov.: 31 AF XY: 0.206 AC XY: 15315 AN XY: 74242

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.230

Alfa AF: 0.0803 Hom.: 135

Bravo AF: 0.223

Asia WGS AF: 0.217 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.80

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: rs12587111; hg19: chr14-68094265;