rs12142335

Positions:

• chr1-107760300-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000370056.9(VAV3):​c.1017+484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,846 control chromosomes in the GnomAD database, including 4,607 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 0.24 (4607 hom., cov: 32)
• Consequence: VAV3 ENST00000370056.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5	c.1017+484C>T		intron_variant		ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9	c.1017+484C>T		intron_variant		1	NM_006113.5	ENSP00000359073	P1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35885 AN: 151728 Hom.: 4608 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.236 AC: 35893 AN: 151846 Hom.: 4607 Cov.: 32 AF XY: 0.236 AC XY: 17514 AN XY: 74224

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.218

Alfa AF: 0.242 Hom.: 9291

Bravo AF: 0.223

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.69

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: rs12142335; hg19: chr1-108302922;