rs4902503

Positions:

• chr14-67632756-A-G

Variant summary

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

The NM_001172.4(ARG2):​c.185-9430A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 149,168 control chromosomes in the GnomAD database, including 18,167 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 0.43 (18167 hom., cov: 27)
• Consequence: ARG2 NM_001172.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756

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:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]

ARG2 (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 (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARG2	NM_001172.4	c.185-9430A>G		intron_variant		ENST00000261783.4	NP_001163.1
GPHN	XM_047430879.1	c.1313-102439A>G		intron_variant			XP_047286835.1
LOC124903331	XR_007064218.1	n.1122-3416T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARG2	ENST00000261783.4	c.185-9430A>G		intron_variant		1	NM_001172.4	ENSP00000261783.3
ARG2	ENST00000556491.1	n.183-9430A>G		intron_variant		5
ARG2	ENST00000557120.5	n.227-9430A>G		intron_variant		2
ENSG00000286861	ENST00000662787.1	n.1084-3416T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.434 AC: 64645 AN: 149054 Hom.: 18111 Cov.: 27

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.434 AC: 64772 AN: 149168 Hom.: 18167 Cov.: 27 AF XY: 0.431 AC XY: 31263 AN XY: 72524

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.449

Alfa AF: 0.364 Hom.: 1667

Bravo AF: 0.470

Asia WGS AF: 0.443 AC: 1542 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	0.74
DANN	Benign	0.70

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: rs4902503; hg19: chr14-68099473;