Variant chr1-107705049-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_006113.5(VAV3):c.1515A>G(p.Arg505=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,611,204 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0080 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 21 hom. )

Consequence

VAV3
NM_006113.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.102

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 1-107705049-T-C is Benign according to our data. Variant chr1-107705049-T-C is described in ClinVar as [Benign]. Clinvar id is 787207.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.102 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00799 (1216/152212) while in subpopulation AFR AF= 0.0264 (1096/41522). AF 95% confidence interval is 0.0251. There are 21 homozygotes in gnomad4. There are 561 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1216 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAV3	NM_006113.5 linkuse as main transcript	c.1515A>G	p.Arg505=	synonymous_variant	16/27	ENST00000370056.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAV3	ENST00000370056.9 linkuse as main transcript	c.1515A>G	p.Arg505=	synonymous_variant	16/27	1	NM_006113.5	P1	Q9UKW4-1

Frequencies

GnomAD3 genomes

AF:

0.00798

AC:

1213

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0264

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00270

AC:

675

AN:

249998

Hom.:

AF XY:

0.00215

AC XY:

291

AN XY:

135064

show subpopulations

Gnomad AFR exome

AF:

0.0269

Gnomad AMR exome

AF:

0.00174

Gnomad ASJ exome

AF:

0.00279

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000965

Gnomad OTH exome

AF:

0.00378

GnomAD4 exome

AF:

0.00145

AC:

2112

AN:

1458992

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

1004

AN XY:

725236

show subpopulations

Gnomad4 AFR exome

AF:

0.0286

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00357

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000697

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000549

Gnomad4 OTH exome

AF:

0.00337

GnomAD4 genome

AF:

0.00799

AC:

1216

AN:

152212

Hom.:

Cov.:

AF XY:

0.00754

AC XY:

561

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0264

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000721

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00436

Hom.:

Bravo

AF:

0.00908

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00137

EpiControl

AF:

0.00143

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.8

DANN

Benign

0.75

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

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