rs17542571

chr1-107764704-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.921+372T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,110 control chromosomes in the GnomAD database, including 1,197 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 0.12 (1197 hom., cov: 32)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV3	NM_006113.5	c.921+372T>A		intron_variant		ENST00000370056.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV3	ENST00000370056.9	c.921+372T>A		intron_variant		1	NM_006113.5	P1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17938 AN: 151992 Hom.: 1196 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.118 AC: 17951 AN: 152110 Hom.: 1197 Cov.: 32 AF XY: 0.112 AC XY: 8345 AN XY: 74344

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0798

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.0938

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.116

Alfa AF: 0.128 Hom.: 149

Bravo AF: 0.119

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	13
Dann	Benign	0.90

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: rs17542571; hg19: chr1-108307326;