rs2010963

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000607600.1(ENSG00000272114):n.4G>C variant causes a non coding transcript exon 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

ENSG00000272114
ENST00000607600.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 1.03

Publications

979 publications found

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 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

VEGFA links:

ENSG00000272114 (HGNC:):

ENSG00000272114 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000607600.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VEGFA	NM_003376.6	MANE Select	c.-94C>G	5_prime_UTR	Exon 1 of 8	NP_003367.4
VEGFA	NM_001025366.3		c.-94C>G	5_prime_UTR	Exon 1 of 8	NP_001020537.2	P15692-14
VEGFA	NM_001025367.3		c.-94C>G	5_prime_UTR	Exon 1 of 8	NP_001020538.2	P15692-16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VEGFA	ENST00000672860.3	MANE Select	c.-94C>G	5_prime_UTR	Exon 1 of 8	ENSP00000500082.3	P15692-13
VEGFA	ENST00000425836.9	TSL:1	c.-94C>G	5_prime_UTR	Exon 1 of 7	ENSP00000388465.4	A0A0A0MSH5
VEGFA	ENST00000372067.8	TSL:1	c.-94C>G	5_prime_UTR	Exon 1 of 7	ENSP00000361137.4	P15692-11

Frequencies

GnomAD3 genomes

AF:

0.682

AC:

103572

AN:

151946

Hom.:

35315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.675

Gnomad AMI

AF:

0.804

Gnomad AMR

AF:

0.654

Gnomad ASJ

AF:

0.589

Gnomad EAS

AF:

0.596

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.770

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.686

Gnomad OTH

AF:

0.651

GnomAD4 exome

AF:

0.684

AC:

886758

AN:

1297288

Hom.:

304109

Cov.:

AF XY:

0.684

AC XY:

436658

AN XY:

638118

show subpopulations

African (AFR)

AF:

0.682

AC:

17853

AN:

26166

American (AMR)

AF:

0.662

AC:

13922

AN:

21040

Ashkenazi Jewish (ASJ)

AF:

0.584

AC:

12178

AN:

20870

East Asian (EAS)

AF:

0.578

AC:

17211

AN:

29752

South Asian (SAS)

AF:

0.729

AC:

49096

AN:

67388

European-Finnish (FIN)

AF:

0.764

AC:

24470

AN:

32024

Middle Eastern (MID)

AF:

0.614

AC:

2896

AN:

4718

European-Non Finnish (NFE)

AF:

0.684

AC:

712359

AN:

1041272

Other (OTH)

AF:

0.680

AC:

36773

AN:

54058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

14388

28777

43165

57554

71942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18792

37584

56376

75168

93960

<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:

0.682

AC:

103677

AN:

152066

Hom.:

35366

Cov.:

AF XY:

0.686

AC XY:

51010

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.675

AC:

28021

AN:

41496

American (AMR)

AF:

0.654

AC:

10000

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

2044

AN:

3470

East Asian (EAS)

AF:

0.596

AC:

3052

AN:

5124

South Asian (SAS)

AF:

0.726

AC:

3507

AN:

4828

European-Finnish (FIN)

AF:

0.770

AC:

8148

AN:

10586

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.686

AC:

46619

AN:

67964

Other (OTH)

AF:

0.649

AC:

1371

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1759

3518

5278

7037

8796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<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:

0.632

Hom.:

1917

Bravo

AF:

0.666

Asia WGS

AF:

0.699

AC:

2435

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Microvascular complications of diabetes, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

1.0

PromoterAI

-0.075

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over