Menu
GeneBe

rs3025039

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003376.6(VEGFA):c.*237C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 701,944 control chromosomes in the GnomAD database, including 7,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

Frequency

Genomes: đť‘“ 0.13 ( 1464 hom., cov: 31)
Exomes đť‘“: 0.15 ( 6449 hom. )

Consequence

VEGFA
NM_003376.6 3_prime_UTR

Scores

2

Clinical Significance

other no assertion criteria provided O:1

Conservation

PhyloP100: 0.0550
Variant links:
Genes affected
VEGFA (HGNC:12680): (vascular endothelial growth factor A) This gene is a member of the PDGF/VEGF growth factor family. It encodes a heparin-binding protein, which exists as a disulfide-linked homodimer. This growth factor induces proliferation and migration of vascular endothelial cells, and is essential for both physiological and pathological angiogenesis. Disruption of this gene in mice resulted in abnormal embryonic blood vessel formation. This gene is upregulated in many known tumors and its expression is correlated with tumor stage and progression. Elevated levels of this protein are found in patients with POEMS syndrome, also known as Crow-Fukase syndrome. Allelic variants of this gene have been associated with microvascular complications of diabetes 1 (MVCD1) and atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been described. There is also evidence for alternative translation initiation from upstream non-AUG (CUG) codons resulting in additional isoforms. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is antiangiogenic. Expression of some isoforms derived from the AUG start codon is regulated by a small upstream open reading frame, which is located within an internal ribosome entry site. The levels of VEGF are increased during infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus promoting inflammation by facilitating recruitment of inflammatory cells, and by increasing the level of angiopoietin II (Ang II), one of two products of the SARS-CoV-2 binding target, angiotensin-converting enzyme 2 (ACE2). In turn, Ang II facilitates the elevation of VEGF, thus forming a vicious cycle in the release of inflammatory cytokines. [provided by RefSeq, Jun 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VEGFANM_003376.6 linkuse as main transcriptc.*237C>T 3_prime_UTR_variant 8/8 ENST00000672860.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VEGFAENST00000672860.3 linkuse as main transcriptc.*237C>T 3_prime_UTR_variant 8/8 NM_003376.6 P15692-13

Frequencies

GnomAD3 genomes
AF:
0.129
AC:
19602
AN:
151728
Hom.:
1462
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0849
Gnomad AMI
AF:
0.0802
Gnomad AMR
AF:
0.176
Gnomad ASJ
AF:
0.132
Gnomad EAS
AF:
0.175
Gnomad SAS
AF:
0.0972
Gnomad FIN
AF:
0.151
Gnomad MID
AF:
0.146
Gnomad NFE
AF:
0.142
Gnomad OTH
AF:
0.127
GnomAD4 exome
AF:
0.146
AC:
80486
AN:
550102
Hom.:
6449
Cov.:
6
AF XY:
0.143
AC XY:
41724
AN XY:
292778
show subpopulations
Gnomad4 AFR exome
AF:
0.0853
Gnomad4 AMR exome
AF:
0.270
Gnomad4 ASJ exome
AF:
0.135
Gnomad4 EAS exome
AF:
0.196
Gnomad4 SAS exome
AF:
0.0975
Gnomad4 FIN exome
AF:
0.149
Gnomad4 NFE exome
AF:
0.142
Gnomad4 OTH exome
AF:
0.138
GnomAD4 genome
AF:
0.129
AC:
19624
AN:
151842
Hom.:
1464
Cov.:
31
AF XY:
0.130
AC XY:
9650
AN XY:
74200
show subpopulations
Gnomad4 AFR
AF:
0.0850
Gnomad4 AMR
AF:
0.176
Gnomad4 ASJ
AF:
0.132
Gnomad4 EAS
AF:
0.175
Gnomad4 SAS
AF:
0.0982
Gnomad4 FIN
AF:
0.151
Gnomad4 NFE
AF:
0.142
Gnomad4 OTH
AF:
0.127
Alfa
AF:
0.141
Hom.:
1927
Bravo
AF:
0.134
Asia WGS
AF:
0.138
AC:
481
AN:
3478

ClinVar

Significance: other
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Cholangiocarcinoma Other:1
other, no assertion criteria providedresearchDepartment of Surgery, Campus Charité Mitte Campus Virchow-klinikum, Charite-Universitaetsmedizin BerlinDec 10, 2022No association with disease-free or overall survival after resection of intrahepatic Cholangiocarcinoma No association with disease-free or overall survival

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
11
Dann
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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.

Other links and lift over

dbSNP: rs3025039; hg19: chr6-43752536; COSMIC: COSV57878013; COSMIC: COSV57878013; API