chr1-107744349-A-G

Position:

• chr1-107744349-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006113.5(VAV3):​c.1502+4619T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,076 control chromosomes in the GnomAD database, including 33,662 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 0.66 (33662 hom., cov: 32)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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]

VAV3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5	c.1502+4619T>C		intron_variant		ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9	c.1502+4619T>C		intron_variant		1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100147 AN: 151958 Hom.: 33624 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.659 AC: 100247 AN: 152076 Hom.: 33662 Cov.: 32 AF XY: 0.666 AC XY: 49482 AN XY: 74352

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.971

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.679

Alfa AF: 0.638 Hom.: 44008

Bravo AF: 0.668

Asia WGS AF: 0.855 AC: 2974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs6583045; hg19: chr1-108286971; COSMIC: COSV58379421;