rs2504458

Variant names:

• chr1-107684739-T-C
• rs2504458
• NM_006113.5:c.1732-1206A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006113.5(VAV3):​c.1732-1206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,062 control chromosomes in the GnomAD database, including 8,479 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 0.33 (8479 hom., cov: 33)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006113.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV3	NM_006113.5	MANE Select	c.1732-1206A>G		intron	N/A	NP_006104.4
	VAV3	NM_001079874.2		c.52-1206A>G		intron	N/A	NP_001073343.1	Q9UKW4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV3	ENST00000370056.9	TSL:1 MANE Select	c.1732-1206A>G		intron	N/A	ENSP00000359073.4	Q9UKW4-1
	VAV3	ENST00000527011.5	TSL:1	c.1732-1206A>G		intron	N/A	ENSP00000432540.1	Q9UKW4-4
	VAV3	ENST00000415432.6	TSL:1	c.52-1206A>G		intron	N/A	ENSP00000394897.2	Q9UKW4-3

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50626 AN: 151944 Hom.: 8458 Cov.: 33

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.333 AC: 50692 AN: 152062 Hom.: 8479 Cov.: 33 AF XY: 0.331 AC XY: 24627 AN XY: 74318

African (AFR) AF: 0.332 AC: 13753 AN: 41482

American (AMR) AF: 0.298 AC: 4551 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1228 AN: 3470

East Asian (EAS) AF: 0.168 AC: 870 AN: 5184

South Asian (SAS) AF: 0.382 AC: 1837 AN: 4814

European-Finnish (FIN) AF: 0.332 AC: 3499 AN: 10550

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23724 AN: 67968

Other (OTH) AF: 0.326 AC: 688 AN: 2110

Alfa AF: 0.340 Hom.: 13174

Bravo AF: 0.328

Asia WGS AF: 0.294 AC: 1022 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.51
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2504458; hg19: chr1-108227361; COSMIC: COSV107447446;