rs7543435

Variant names:

• chr1-107660088-A-G
• rs7543435
• NM_006113.5:c.1778-17333T>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.1778-17333T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,974 control chromosomes in the GnomAD database, including 26,517 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 0.58 (26517 hom., cov: 31)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV3	NM_006113.5	c.1778-17333T>C		intron_variant	Intron 19 of 26	ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9	c.1778-17333T>C		intron_variant	Intron 19 of 26	1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88064 AN: 151856 Hom.: 26483 Cov.: 31

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.580 AC: 88148 AN: 151974 Hom.: 26517 Cov.: 31 AF XY: 0.570 AC XY: 42345 AN XY: 74274

African (AFR) AF: 0.754 AC: 31279 AN: 41470

American (AMR) AF: 0.537 AC: 8194 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1937 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2026 AN: 5136

South Asian (SAS) AF: 0.460 AC: 2216 AN: 4820

European-Finnish (FIN) AF: 0.421 AC: 4450 AN: 10564

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36134 AN: 67954

Other (OTH) AF: 0.573 AC: 1209 AN: 2110

Alfa AF: 0.552 Hom.: 75258

Bravo AF: 0.596

Asia WGS AF: 0.457 AC: 1592 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	7.1
DANN	Benign	0.65
PhyloP100		0.62
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: rs7543435; hg19: chr1-108202710; COSMIC: COSV58379179;