rs7543435

Positions:

• chr1-107660088-A-G

Variant summary

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

The NM_006113.5(VAV3):​c.1778-17333T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,974 control chromosomes in the GnomAD database, including 26,517 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 0.58 (26517 hom., cov: 31)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621

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 (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5	c.1778-17333T>C		intron_variant		ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9	c.1778-17333T>C		intron_variant		1	NM_006113.5	ENSP00000359073	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88064 AN: 151856 Hom.: 26483 Cov.: 31

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.580 AC: 88148 AN: 151974 Hom.: 26517 Cov.: 31 AF XY: 0.570 AC XY: 42345 AN XY: 74274

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.573

Alfa AF: 0.541 Hom.: 45625

Bravo AF: 0.596

Asia WGS AF: 0.457 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.1
DANN	Benign	0.65

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: rs7543435; hg19: chr1-108202710; COSMIC: COSV58379179;