rs2504458

Positions:

• chr1-107684739-T-C

Variant summary

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

The NM_006113.5(VAV3):​c.1732-1206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,062 control chromosomes in the GnomAD database, including 8,479 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 0.33 (8479 hom., cov: 33)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5	c.1732-1206A>G		intron_variant		ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9	c.1732-1206A>G		intron_variant		1	NM_006113.5	ENSP00000359073	P1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50626 AN: 151944 Hom.: 8458 Cov.: 33

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.333 AC: 50692 AN: 152062 Hom.: 8479 Cov.: 33 AF XY: 0.331 AC XY: 24627 AN XY: 74318

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.326

Alfa AF: 0.345 Hom.: 9241

Bravo AF: 0.328

Asia WGS AF: 0.294 AC: 1022 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.51

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: rs2504458; hg19: chr1-108227361;