chr14-67648284-A-G

Position:

• chr14-67648284-A-G

Variant summary

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

The NM_006370.3(VTI1B):​c.*3101T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,362,416 control chromosomes in the GnomAD database, including 55,030 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 (4278 hom., cov: 32)
  • Exomes 𝑓: 0.28 (50752 hom.)
• Consequence: VTI1B NM_006370.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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: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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VTI1B	NM_006370.3	c.*3101T>C		3_prime_UTR_variant	6/6	ENST00000554659.6	NP_006361.1
ARG2	NM_001172.4	c.859+101A>G		intron_variant		ENST00000261783.4	NP_001163.1
GPHN	XM_047430879.1	c.1313-86911A>G		intron_variant			XP_047286835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VTI1B	ENST00000554659.6	c.*3101T>C		3_prime_UTR_variant	6/6	1	NM_006370.3	ENSP00000450731.1
ARG2	ENST00000261783.4	c.859+101A>G		intron_variant		1	NM_001172.4	ENSP00000261783.3
ARG2	ENST00000557319.1	n.533+101A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31728 AN: 152038 Hom.: 4280 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.0951

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.276 AC: 333927 AN: 1210260 Hom.: 50752 Cov.: 16 AF XY: 0.272 AC XY: 162923 AN XY: 598060

Gnomad4 AFR exome AF: 0.0446

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.0226

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.209 AC: 31725 AN: 152156 Hom.: 4278 Cov.: 32 AF XY: 0.203 AC XY: 15111 AN XY: 74370

Gnomad4 AFR AF: 0.0601

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.0954

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.199

Alfa AF: 0.279 Hom.: 7886

Bravo AF: 0.196

Asia WGS AF: 0.0620 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.7
DANN	Benign	0.81

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: rs3742879; hg19: chr14-68115001;