14-67648284-A-G

Variant names:

• chr14-67648284-A-G
• rs3742879
• NM_006370.3:c.*3101T>C

Variant summary

Our verdict is Benign. The variant received -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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VTI1B	NM_006370.3	c.*3101T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000554659.6	NP_006361.1
ARG2	NM_001172.4	c.859+101A>G		intron_variant	Intron 7 of 7	ENST00000261783.4	NP_001163.1
GPHN	XM_047430879.1	c.1313-86911A>G		intron_variant	Intron 14 of 14		XP_047286835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTI1B	ENST00000554659	c.*3101T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_006370.3	ENSP00000450731.1
ARG2	ENST00000261783.4	c.859+101A>G		intron_variant	Intron 7 of 7	1	NM_001172.4	ENSP00000261783.3
ARG2	ENST00000557319.1	n.533+101A>G		intron_variant	Intron 3 of 3	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 AC: 1209 AN: 27114

Gnomad4 AMR exome AF: 0.234 AC: 6053 AN: 25896

Gnomad4 ASJ exome AF: 0.206 AC: 4025 AN: 19570

Gnomad4 EAS exome AF: 0.0226 AC: 829 AN: 36698

Gnomad4 SAS exome AF: 0.100 AC: 6141 AN: 61160

Gnomad4 FIN exome AF: 0.265 AC: 10612 AN: 40058

Gnomad4 NFE exome AF: 0.309 AC: 291897 AN: 944362

Gnomad4 Remaining exome AF: 0.246 AC: 12498 AN: 50834

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 AC: 0.0600982 AN: 0.0600982

Gnomad4 AMR AF: 0.214 AC: 0.213715 AN: 0.213715

Gnomad4 ASJ AF: 0.220 AC: 0.219758 AN: 0.219758

Gnomad4 EAS AF: 0.0152 AC: 0.0152099 AN: 0.0152099

Gnomad4 SAS AF: 0.0954 AC: 0.0954056 AN: 0.0954056

Gnomad4 FIN AF: 0.260 AC: 0.259841 AN: 0.259841

Gnomad4 NFE AF: 0.312 AC: 0.312301 AN: 0.312301

Gnomad4 OTH AF: 0.199 AC: 0.199337 AN: 0.199337

Alfa AF: 0.271 Hom.: 16723

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
Mutation Taster		=100/0	polymorphism (auto)

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;