rs11803410

Variant names:

• chr1-107598856-G-A
• rs11803410
• NM_006113.5:c.2221-2515C>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.2221-2515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,640 control chromosomes in the GnomAD database, including 10,094 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 0.36 (10094 hom., cov: 31)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006113.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV3	NM_006113.5	MANE Select	c.2221-2515C>T		intron	N/A	NP_006104.4
	VAV3	NM_001079874.2		c.541-2515C>T		intron	N/A	NP_001073343.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV3	ENST00000370056.9	TSL:1 MANE Select	c.2221-2515C>T		intron	N/A	ENSP00000359073.4
	VAV3	ENST00000527011.5	TSL:1	c.2221-2515C>T		intron	N/A	ENSP00000432540.1
	VAV3	ENST00000415432.6	TSL:1	c.541-2515C>T		intron	N/A	ENSP00000394897.2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54429 AN: 151524 Hom.: 10097 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.359 AC: 54435 AN: 151640 Hom.: 10094 Cov.: 31 AF XY: 0.364 AC XY: 26964 AN XY: 74082

African (AFR) AF: 0.278 AC: 11493 AN: 41336

American (AMR) AF: 0.338 AC: 5150 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1435 AN: 3458

East Asian (EAS) AF: 0.380 AC: 1958 AN: 5146

South Asian (SAS) AF: 0.289 AC: 1390 AN: 4804

European-Finnish (FIN) AF: 0.501 AC: 5238 AN: 10460

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26600 AN: 67880

Other (OTH) AF: 0.372 AC: 784 AN: 2106

Alfa AF: 0.362 Hom.: 1792

Bravo AF: 0.349

Asia WGS AF: 0.286 AC: 993 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		-0.044
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: rs11803410; hg19: chr1-108141478;