Variant rs3025039 details in Genebe, Genetics Data Aggregator

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: 𝑓 0.13 ( 1464 hom., cov: 31)

Exomes 𝑓: 0.15 ( 6449 hom. )

Consequence

VEGFA
NM_003376.6 3_prime_UTR

Scores

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]

VEGFA links:

POLR1C (HGNC:):

POLR1C links:

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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	Protein	UniProt
VEGFA	NM_003376.6 linkuse as main transcript	c.*237C>T		3_prime_UTR_variant	8/8	ENST00000672860.3	NP_003367.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFA	ENST00000672860.3 linkuse as main transcript	c.*237C>T		3_prime_UTR_variant	8/8		NM_003376.6	ENSP00000500082		P15692-13

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19602

AN:

151728

Hom.:

1462

Cov.:

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.:

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.:

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 provided

research

Department of Surgery, Campus Charité Mitte Campus Virchow-klinikum, Charite-Universitaetsmedizin Berlin

Dec 10, 2022

No 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

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.

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