rs345299

Positions:

• chr1-107905511-A-C
• chr1-107905511-A-G
• chr1-107905511-A-T

Variant summary

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

The NM_006113.5(VAV3):​c.205-30494T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,996 control chromosomes in the GnomAD database, including 37,621 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 0.69 (37621 hom., cov: 31)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.903

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5	c.205-30494T>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.205-30494T>G		intron_variant		1	NM_006113.5	ENSP00000359073	P1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104124 AN: 151878 Hom.: 37574 Cov.: 31

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.686 AC: 104228 AN: 151996 Hom.: 37621 Cov.: 31 AF XY: 0.686 AC XY: 50946 AN XY: 74282

Gnomad4 AFR AF: 0.921

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.665

Alfa AF: 0.598 Hom.: 28707

Bravo AF: 0.693

Asia WGS AF: 0.775 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.80
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: rs345299; hg19: chr1-108448133;