rs17542571

Variant names:

• chr1-107764704-A-T
• rs17542571
• NM_006113.5:c.921+372T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006113.5(VAV3):​c.921+372T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,110 control chromosomes in the GnomAD database, including 1,197 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 0.12 (1197 hom., cov: 32)
• Consequence: VAV3 NM_006113.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 0 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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 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.921+372T>A		intron	N/A	NP_006104.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV3	ENST00000370056.9	TSL:1 MANE Select	c.921+372T>A		intron	N/A	ENSP00000359073.4
	VAV3	ENST00000527011.5	TSL:1	c.921+372T>A		intron	N/A	ENSP00000432540.1
	VAV3	ENST00000343258.8	TSL:1	n.767+372T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17938 AN: 151992 Hom.: 1196 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.118 AC: 17951 AN: 152110 Hom.: 1197 Cov.: 32 AF XY: 0.112 AC XY: 8345 AN XY: 74344

African (AFR) AF: 0.126 AC: 5218 AN: 41500

American (AMR) AF: 0.0798 AC: 1220 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3468

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5170

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4814

European-Finnish (FIN) AF: 0.0938 AC: 992 AN: 10578

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9417 AN: 67984

Other (OTH) AF: 0.116 AC: 244 AN: 2112

Alfa AF: 0.128 Hom.: 149

Bravo AF: 0.119

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		0.18
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: rs17542571; hg19: chr1-108307326;