rs4915077

chr1-107823394-T-Cchr1-107823394-T-G

Variant summary

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

The NM_006113.5(VAV3):c.322-43902A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 152,200 control chromosomes in the GnomAD database, including 848 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 0.094 (848 hom., cov: 32)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV3	NM_006113.5	c.322-43902A>G		intron_variant		ENST00000370056.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV3	ENST00000370056.9	c.322-43902A>G		intron_variant		1	NM_006113.5	P1

Frequencies

GnomAD3 genomes AF: 0.0935 AC: 14216 AN: 152082 Hom.: 848 Cov.: 32

Gnomad AFR AF: 0.0552

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0859

Gnomad OTH AF: 0.0756

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

GnomAD4 genome AF: 0.0935 AC: 14231 AN: 152200 Hom.: 848 Cov.: 32 AF XY: 0.0973 AC XY: 7239 AN XY: 74428

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0859

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0909 Hom.: 950

Bravo AF: 0.0969

Asia WGS AF: 0.191 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.77

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: rs4915077; hg19: chr1-108366016;