rs10494076

Variant names:

• chr1-107795705-A-G
• rs10494076
• NM_006113.5:c.322-16213T>C

Variant summary

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

The NM_006113.5(VAV3):​c.322-16213T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,214 control chromosomes in the GnomAD database, including 7,834 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 0.31 (7834 hom., cov: 33)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 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.322-16213T>C		intron	N/A	NP_006104.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV3	ENST00000370056.9	TSL:1 MANE Select	c.322-16213T>C		intron	N/A	ENSP00000359073.4	Q9UKW4-1
	VAV3	ENST00000527011.5	TSL:1	c.322-16213T>C		intron	N/A	ENSP00000432540.1	Q9UKW4-4
	VAV3	ENST00000923907.1		c.322-16213T>C		intron	N/A	ENSP00000593966.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46828 AN: 152096 Hom.: 7841 Cov.: 33

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0294

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.308 AC: 46830 AN: 152214 Hom.: 7834 Cov.: 33 AF XY: 0.305 AC XY: 22717 AN XY: 74422

African (AFR) AF: 0.255 AC: 10589 AN: 41516

American (AMR) AF: 0.243 AC: 3720 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 858 AN: 3472

East Asian (EAS) AF: 0.0299 AC: 155 AN: 5184

South Asian (SAS) AF: 0.197 AC: 949 AN: 4826

European-Finnish (FIN) AF: 0.390 AC: 4135 AN: 10602

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25474 AN: 67994

Other (OTH) AF: 0.298 AC: 631 AN: 2116

Alfa AF: 0.345 Hom.: 4749

Bravo AF: 0.291

Asia WGS AF: 0.139 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.71
PhyloP100		0.040
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: rs10494076; hg19: chr1-108338327;