rs7521681

Variant names:

• chr1-107779913-G-A
• rs7521681
• NM_006113.5:c.322-421C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-107779913-G-A
• chr1-107779913-G-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.322-421C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,068 control chromosomes in the GnomAD database, including 2,047 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 0.16 (2047 hom., cov: 32)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAV3	NM_006113.5	c.322-421C>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.322-421C>T		intron_variant	Intron 2 of 26	1	NM_006113.5	ENSP00000359073.4

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23859 AN: 151950 Hom.: 2047 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0925

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.157 AC: 23865 AN: 152068 Hom.: 2047 Cov.: 32 AF XY: 0.159 AC XY: 11799 AN XY: 74308

African (AFR) AF: 0.133 AC: 5502 AN: 41494

American (AMR) AF: 0.176 AC: 2681 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 612 AN: 3470

East Asian (EAS) AF: 0.350 AC: 1808 AN: 5162

South Asian (SAS) AF: 0.114 AC: 547 AN: 4808

European-Finnish (FIN) AF: 0.146 AC: 1542 AN: 10570

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10661 AN: 67976

Other (OTH) AF: 0.179 AC: 377 AN: 2110

Alfa AF: 0.154 Hom.: 2520

Bravo AF: 0.158

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.28
PhyloP100		0.098
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: rs7521681; hg19: chr1-108322535;