rs17020124

Variant names:

• chr1-107815389-G-A
• rs17020124
• NM_006113.5:c.322-35897C>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.322-35897C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 152,200 control chromosomes in the GnomAD database, including 841 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 0.093 (841 hom., cov: 32)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV3	NM_006113.5	c.322-35897C>T		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.322-35897C>T		intron_variant	Intron 2 of 26	1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14153 AN: 152082 Hom.: 841 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0868

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0749

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

GnomAD4 genome AF: 0.0931 AC: 14168 AN: 152200 Hom.: 841 Cov.: 32 AF XY: 0.0967 AC XY: 7199 AN XY: 74410

African (AFR) AF: 0.0547 AC: 2270 AN: 41512

American (AMR) AF: 0.155 AC: 2370 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 301 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5168

South Asian (SAS) AF: 0.133 AC: 641 AN: 4830

European-Finnish (FIN) AF: 0.113 AC: 1200 AN: 10596

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0857 AC: 5832 AN: 68022

Other (OTH) AF: 0.0770 AC: 162 AN: 2104

Alfa AF: 0.0913 Hom.: 89

Bravo AF: 0.0966

Asia WGS AF: 0.184 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.32
PhyloP100		0.24
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: rs17020124; hg19: chr1-108358011;