1-107572523-T-C

Position:

• chr1-107572523-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006113.5(VAV3):​c.*808A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,666 control chromosomes in the GnomAD database, including 62,546 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 0.90 (62343 hom., cov: 32)
  • Exomes 𝑓: 0.96 (203 hom.)
• Consequence: VAV3 NM_006113.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5	c.*808A>G		3_prime_UTR_variant	27/27	ENST00000370056.9	NP_006104.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056	c.*808A>G		3_prime_UTR_variant	27/27	1	NM_006113.5	ENSP00000359073.4
VAV3	ENST00000527011	c.*808A>G		3_prime_UTR_variant	28/28	1		ENSP00000432540.1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137374 AN: 152112 Hom.: 62312 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.933

Gnomad OTH AF: 0.914

GnomAD4 exome AF: 0.963 AC: 420 AN: 436 Hom.: 203 Cov.: 0 AF XY: 0.966 AC XY: 255 AN XY: 264

Gnomad4 FIN exome AF: 0.962

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.903 AC: 137461 AN: 152230 Hom.: 62343 Cov.: 32 AF XY: 0.906 AC XY: 67414 AN XY: 74430

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.933

Gnomad4 OTH AF: 0.915

Alfa AF: 0.927 Hom.: 62068

Bravo AF: 0.899

Asia WGS AF: 0.957 AC: 3329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.18
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs2769668; hg19: chr1-108115145;