rs2010963
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_003376.6(VEGFA):c.-94C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,449,354 control chromosomes in the GnomAD database, including 339,475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.68 ( 35366 hom., cov: 33)
Exomes 𝑓: 0.68 ( 304109 hom. )
Consequence
VEGFA
NM_003376.6 5_prime_UTR
NM_003376.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.03
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 6-43770613-C-G is Benign according to our data. Variant chr6-43770613-C-G is described in ClinVar as [Benign]. Clinvar id is 12223.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VEGFA | NM_003376.6 | c.-94C>G | 5_prime_UTR_variant | 1/8 | ENST00000672860.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VEGFA | ENST00000672860.3 | c.-94C>G | 5_prime_UTR_variant | 1/8 | NM_003376.6 | ||||
ENST00000607600.1 | n.4G>C | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.682 AC: 103572AN: 151946Hom.: 35315 Cov.: 33
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GnomAD4 exome AF: 0.684 AC: 886758AN: 1297288Hom.: 304109 Cov.: 57 AF XY: 0.684 AC XY: 436658AN XY: 638118
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GnomAD4 genome ? AF: 0.682 AC: 103677AN: 152066Hom.: 35366 Cov.: 33 AF XY: 0.686 AC XY: 51010AN XY: 74322
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ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2021 | This variant is associated with the following publications: (PMID: 27648002, 25992764, 23957473, 25328912, 22993299, 15338501, 11978667, 24205329, 23007030, 16142870, 19653005, 23353010, 10930302, 15963467) - |
Microvascular complications of diabetes, susceptibility to, 1 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | May 01, 2002 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at