chr1-107959790-C-A

Variant names:

• chr1-107959790-C-A
• rs2801219
• NM_006113.5:c.204+4876G>T

Variant summary

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

The NM_006113.5(VAV3):​c.204+4876G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,006 control chromosomes in the GnomAD database, including 32,386 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 0.63 (32386 hom., cov: 31)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV3	NM_006113.5	c.204+4876G>T		intron_variant	Intron 1 of 26	ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9	c.204+4876G>T		intron_variant	Intron 1 of 26	1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95271 AN: 151888 Hom.: 32388 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.627 AC: 95298 AN: 152006 Hom.: 32386 Cov.: 31 AF XY: 0.629 AC XY: 46743 AN XY: 74298

African (AFR) AF: 0.331 AC: 13712 AN: 41418

American (AMR) AF: 0.754 AC: 11516 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2519 AN: 3472

East Asian (EAS) AF: 0.768 AC: 3974 AN: 5174

South Asian (SAS) AF: 0.674 AC: 3250 AN: 4820

European-Finnish (FIN) AF: 0.725 AC: 7671 AN: 10574

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50278 AN: 67964

Other (OTH) AF: 0.687 AC: 1450 AN: 2110

Alfa AF: 0.667 Hom.: 5609

Bravo AF: 0.620

Asia WGS AF: 0.696 AC: 2419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.50
PhyloP100		0.26
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: rs2801219; hg19: chr1-108502412;