rs12142335

Variant names:

• chr1-107760300-G-A
• rs12142335
• NM_006113.5:c.1017+484C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006113.5(VAV3):​c.1017+484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,846 control chromosomes in the GnomAD database, including 4,607 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 0.24 (4607 hom., cov: 32)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV3	NM_006113.5	c.1017+484C>T		intron_variant	Intron 10 of 26	ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9	c.1017+484C>T		intron_variant	Intron 10 of 26	1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35885 AN: 151728 Hom.: 4608 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.236 AC: 35893 AN: 151846 Hom.: 4607 Cov.: 32 AF XY: 0.236 AC XY: 17514 AN XY: 74224

African (AFR) AF: 0.239 AC: 9884 AN: 41392

American (AMR) AF: 0.167 AC: 2552 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 595 AN: 3468

East Asian (EAS) AF: 0.0226 AC: 117 AN: 5172

South Asian (SAS) AF: 0.137 AC: 659 AN: 4820

European-Finnish (FIN) AF: 0.327 AC: 3445 AN: 10534

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17955 AN: 67886

Other (OTH) AF: 0.218 AC: 460 AN: 2112

Alfa AF: 0.243 Hom.: 20896

Bravo AF: 0.223

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.69
PhyloP100		0.81
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: rs12142335; hg19: chr1-108302922;