rs10494076

Positions:

• chr1-107795705-A-G

Variant summary

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

The NM_006113.5(VAV3):​c.322-16213T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,214 control chromosomes in the GnomAD database, including 7,834 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 0.31 (7834 hom., cov: 33)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

Genes affected

VAV3 (HGNC:12659): (vav guanine nucleotide exchange factor 3) This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. This gene product acts as a GEF preferentially for RhoG, RhoA, and to a lesser extent, RAC1, and it associates maximally with the nucleotide-free states of these GTPases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

VAV3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5	c.322-16213T>C		intron_variant		ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9	c.322-16213T>C		intron_variant		1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46828 AN: 152096 Hom.: 7841 Cov.: 33

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0294

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.308 AC: 46830 AN: 152214 Hom.: 7834 Cov.: 33 AF XY: 0.305 AC XY: 22717 AN XY: 74422

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0299

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.298

Alfa AF: 0.343 Hom.: 4205

Bravo AF: 0.291

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.71

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: rs10494076; hg19: chr1-108338327;