rs345275

Positions:

• chr1-107951181-T-A
• chr1-107951181-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.204+13485A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,096 control chromosomes in the GnomAD database, including 49,675 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 0.78 (49675 hom., cov: 31)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5	c.204+13485A>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.204+13485A>T		intron_variant		1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118368 AN: 151978 Hom.: 49662 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.779 AC: 118418 AN: 152096 Hom.: 49675 Cov.: 31 AF XY: 0.782 AC XY: 58154 AN XY: 74364

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.919

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.924

Gnomad4 FIN AF: 0.913

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.812

Alfa AF: 0.838 Hom.: 6944

Bravo AF: 0.758

Asia WGS AF: 0.845 AC: 2938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.81

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: rs345275; hg19: chr1-108493803;