rs345275

Variant names:

• chr1-107951181-T-A
• rs345275
• NM_006113.5:c.204+13485A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-107951181-T-A
• chr1-107951181-T-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.204+13485A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,096 control chromosomes in the GnomAD database, including 49,675 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 0.78 (49675 hom., cov: 31)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV3	NM_006113.5	c.204+13485A>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+13485A>T		intron_variant	Intron 1 of 26	1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118368 AN: 151978 Hom.: 49662 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.779 AC: 118418 AN: 152096 Hom.: 49675 Cov.: 31 AF XY: 0.782 AC XY: 58154 AN XY: 74364

African (AFR) AF: 0.433 AC: 17946 AN: 41428

American (AMR) AF: 0.878 AC: 13413 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 3192 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4090 AN: 5166

South Asian (SAS) AF: 0.924 AC: 4450 AN: 4816

European-Finnish (FIN) AF: 0.913 AC: 9684 AN: 10602

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62857 AN: 68018

Other (OTH) AF: 0.812 AC: 1714 AN: 2112

Alfa AF: 0.838 Hom.: 6944

Bravo AF: 0.758

Asia WGS AF: 0.845 AC: 2938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.81
PhyloP100		-0.34
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: rs345275; hg19: chr1-108493803;