chr1-107642687-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006113.5(VAV3):​c.1846C>T​(p.Pro616Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,612,830 control chromosomes in the GnomAD database, including 14,511 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1064 hom., cov: 32)
Exomes 𝑓: 0.13 ( 13447 hom. )

Consequence

VAV3
NM_006113.5 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.08

Publications

22 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.002140373).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VAV3NM_006113.5 linkc.1846C>T p.Pro616Ser missense_variant Exon 20 of 27 ENST00000370056.9 NP_006104.4 Q9UKW4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VAV3ENST00000370056.9 linkc.1846C>T p.Pro616Ser missense_variant Exon 20 of 27 1 NM_006113.5 ENSP00000359073.4 Q9UKW4-1

Frequencies

GnomAD3 genomes
AF:
0.111
AC:
16828
AN:
151900
Hom.:
1062
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0622
Gnomad AMI
AF:
0.136
Gnomad AMR
AF:
0.151
Gnomad ASJ
AF:
0.117
Gnomad EAS
AF:
0.201
Gnomad SAS
AF:
0.214
Gnomad FIN
AF:
0.0771
Gnomad MID
AF:
0.0791
Gnomad NFE
AF:
0.121
Gnomad OTH
AF:
0.130
GnomAD2 exomes
AF:
0.137
AC:
34379
AN:
250354
AF XY:
0.139
show subpopulations
Gnomad AFR exome
AF:
0.0610
Gnomad AMR exome
AF:
0.174
Gnomad ASJ exome
AF:
0.114
Gnomad EAS exome
AF:
0.206
Gnomad FIN exome
AF:
0.0794
Gnomad NFE exome
AF:
0.123
Gnomad OTH exome
AF:
0.133
GnomAD4 exome
AF:
0.131
AC:
191521
AN:
1460814
Hom.:
13447
Cov.:
32
AF XY:
0.133
AC XY:
96355
AN XY:
726698
show subpopulations
African (AFR)
AF:
0.0606
AC:
2023
AN:
33404
American (AMR)
AF:
0.172
AC:
7672
AN:
44584
Ashkenazi Jewish (ASJ)
AF:
0.112
AC:
2931
AN:
26102
East Asian (EAS)
AF:
0.241
AC:
9545
AN:
39652
South Asian (SAS)
AF:
0.199
AC:
17159
AN:
86142
European-Finnish (FIN)
AF:
0.0814
AC:
4347
AN:
53408
Middle Eastern (MID)
AF:
0.128
AC:
738
AN:
5750
European-Non Finnish (NFE)
AF:
0.125
AC:
139280
AN:
1111432
Other (OTH)
AF:
0.130
AC:
7826
AN:
60340
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.447
Heterozygous variant carriers
0
9118
18236
27355
36473
45591
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
5214
10428
15642
20856
26070
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.111
AC:
16845
AN:
152016
Hom.:
1064
Cov.:
32
AF XY:
0.112
AC XY:
8304
AN XY:
74316
show subpopulations
African (AFR)
AF:
0.0621
AC:
2577
AN:
41494
American (AMR)
AF:
0.152
AC:
2313
AN:
15244
Ashkenazi Jewish (ASJ)
AF:
0.117
AC:
405
AN:
3464
East Asian (EAS)
AF:
0.202
AC:
1036
AN:
5138
South Asian (SAS)
AF:
0.214
AC:
1025
AN:
4800
European-Finnish (FIN)
AF:
0.0771
AC:
817
AN:
10600
Middle Eastern (MID)
AF:
0.0884
AC:
26
AN:
294
European-Non Finnish (NFE)
AF:
0.121
AC:
8246
AN:
67962
Other (OTH)
AF:
0.131
AC:
276
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
727
1454
2180
2907
3634
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
194
388
582
776
970
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.124
Hom.:
3517
Bravo
AF:
0.114
TwinsUK
AF:
0.131
AC:
487
ALSPAC
AF:
0.122
AC:
469
ESP6500AA
AF:
0.0679
AC:
299
ESP6500EA
AF:
0.124
AC:
1069
ExAC
AF:
0.136
AC:
16516
Asia WGS
AF:
0.211
AC:
736
AN:
3478
EpiCase
AF:
0.127
EpiControl
AF:
0.130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.67
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
21
DANN
Benign
0.20
DEOGEN2
Benign
0.085
T;.;.
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.50
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.57
T;T;T
MetaRNN
Benign
0.0021
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;L;.
PhyloP100
3.1
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.3
N;N;N
REVEL
Benign
0.048
Sift
Benign
0.48
T;T;T
Sift4G
Benign
0.27
T;T;T
Polyphen
0.018
B;.;B
Vest4
0.20
MPC
0.20
ClinPred
0.0035
T
GERP RS
3.8
Varity_R
0.034
gMVP
0.33
Mutation Taster
=98/2
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

Publications

Other links and lift over

dbSNP: rs12410676; hg19: chr1-108185309; COSMIC: COSV58382496; API