1-107581063-C-T

Variant names:

• chr1-107581063-C-T
• rs1410403
• NM_006113.5:c.2351-6865G>A

Variant summary

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

The NM_006113.5(VAV3):​c.2351-6865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,150 control chromosomes in the GnomAD database, including 41,398 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 0.74 (41398 hom., cov: 32)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV3	NM_006113.5	c.2351-6865G>A		intron_variant	Intron 25 of 26	ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9	c.2351-6865G>A		intron_variant	Intron 25 of 26	1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111796 AN: 152032 Hom.: 41365 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.735 AC: 111883 AN: 152150 Hom.: 41398 Cov.: 32 AF XY: 0.739 AC XY: 55002 AN XY: 74394

African (AFR) AF: 0.661 AC: 27417 AN: 41492

American (AMR) AF: 0.735 AC: 11222 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2826 AN: 3470

East Asian (EAS) AF: 0.735 AC: 3805 AN: 5174

South Asian (SAS) AF: 0.659 AC: 3179 AN: 4824

European-Finnish (FIN) AF: 0.854 AC: 9058 AN: 10602

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51893 AN: 67996

Other (OTH) AF: 0.730 AC: 1541 AN: 2110

Alfa AF: 0.750 Hom.: 10343

Bravo AF: 0.723

Asia WGS AF: 0.669 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.088
DANN	Benign	0.45
PhyloP100		-1.6
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: rs1410403; hg19: chr1-108123685;