rs10483801

Positions:

• chr14-67650289-C-A

Variant summary

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

The NM_006370.3(VTI1B):​c.*1096G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 223,168 control chromosomes in the GnomAD database, including 7,355 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 0.26 (5645 hom., cov: 32)
  • Exomes 𝑓: 0.20 (1710 hom.)
• Consequence: VTI1B NM_006370.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

Genes affected

VTI1B (HGNC:17793): (vesicle transport through interaction with t-SNAREs 1B) Enables SNARE binding activity and chloride channel inhibitor activity. Involved in regulation of protein localization to plasma membrane. Located in several cellular components, including endosome membrane; lysosomal membrane; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VTI1B	NM_006370.3	c.*1096G>T		3_prime_UTR_variant	6/6	ENST00000554659.6	NP_006361.1
ARG2	NM_001172.4	c.860-426C>A		intron_variant		ENST00000261783.4	NP_001163.1
GPHN	XM_047430879.1	c.1313-84906C>A		intron_variant			XP_047286835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VTI1B	ENST00000554659.6	c.*1096G>T		3_prime_UTR_variant	6/6	1	NM_006370.3	ENSP00000450731	P1
ARG2	ENST00000261783.4	c.860-426C>A		intron_variant		1	NM_001172.4	ENSP00000261783	P1
ARG2	ENST00000557319.1	n.534-426C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38901 AN: 151872 Hom.: 5623 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.199 AC: 14193 AN: 71178 Hom.: 1710 Cov.: 0 AF XY: 0.195 AC XY: 7125 AN XY: 36498

Gnomad4 AFR exome AF: 0.353

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.440

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.257 AC: 38987 AN: 151990 Hom.: 5645 Cov.: 32 AF XY: 0.256 AC XY: 18981 AN XY: 74266

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.258

Alfa AF: 0.183 Hom.: 1594

Bravo AF: 0.278

Asia WGS AF: 0.347 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.38

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: rs10483801; hg19: chr14-68117006;