Variant 1-107574039-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006113.5(VAV3):c.2502+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,613,466 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 57 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 86 hom. )

Consequence

VAV3
NM_006113.5 splice_region, intron

Scores

Splicing: ADA: 0.00007108

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.719

Variant links:

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]

VAV3 links:

VAV3 (HGNC:):

VAV3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-107574039-C-T is Benign according to our data. Variant chr1-107574039-C-T is described in ClinVar as [Benign]. Clinvar id is 717806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAV3	NM_006113.5 linkuse as main transcript	c.2502+8G>A		splice_region_variant, intron_variant		ENST00000370056.9	NP_006104.4	Q9UKW4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAV3	ENST00000370056.9 linkuse as main transcript	c.2502+8G>A		splice_region_variant, intron_variant		1	NM_006113.5	ENSP00000359073.4		Q9UKW4-1

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2505

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0538

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00949

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00910

GnomAD3 exomes

AF:

0.00658

AC:

1650

AN:

250700

Hom.:

AF XY:

0.00601

AC XY:

814

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.0560

Gnomad AMR exome

AF:

0.00521

Gnomad ASJ exome

AF:

0.000798

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0150

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000538

Gnomad OTH exome

AF:

0.00506

GnomAD4 exome

AF:

0.00290

AC:

4234

AN:

1461236

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

2244

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.0569

Gnomad4 AMR exome

AF:

0.00496

Gnomad4 ASJ exome

AF:

0.000805

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0147

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000384

Gnomad4 OTH exome

AF:

0.00583

GnomAD4 genome

AF:

0.0165

AC:

2511

AN:

152230

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1242

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0538

Gnomad4 AMR

AF:

0.00948

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00909

Hom.:

Bravo

AF:

0.0184

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.000873

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.84

DANN

Benign

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000071

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over