1-107813156-T-C

Variant names:

• chr1-107813156-T-C
• rs10494078
• NM_006113.5:c.322-33664A>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.322-33664A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 150,900 control chromosomes in the GnomAD database, including 34,724 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 0.67 (34724 hom., cov: 29)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV3	NM_006113.5	c.322-33664A>G		intron_variant	Intron 2 of 26	ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9	c.322-33664A>G		intron_variant	Intron 2 of 26	1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.674 AC: 101582 AN: 150800 Hom.: 34699 Cov.: 29

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.674 AC: 101659 AN: 150900 Hom.: 34724 Cov.: 29 AF XY: 0.666 AC XY: 49058 AN XY: 73614

African (AFR) AF: 0.691 AC: 28360 AN: 41022

American (AMR) AF: 0.601 AC: 9139 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2374 AN: 3460

East Asian (EAS) AF: 0.333 AC: 1708 AN: 5122

South Asian (SAS) AF: 0.583 AC: 2793 AN: 4792

European-Finnish (FIN) AF: 0.644 AC: 6517 AN: 10124

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48591 AN: 67864

Other (OTH) AF: 0.639 AC: 1341 AN: 2100

Alfa AF: 0.693 Hom.: 19920

Bravo AF: 0.669

Asia WGS AF: 0.509 AC: 1769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.67
PhyloP100		-2.9
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: rs10494078; hg19: chr1-108355778;