Genetic Variant VEGFB:p.Asp136Glu (chr11-64237220-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003377.5(VEGFB):c.408C>G(p.Asp136Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D136D) has been classified as Benign.

Frequency

Genomes: not found (cov: 28)

Consequence

VEGFB
NM_003377.5 missense, splice_region

Scores

Splicing: ADA: 0.01924

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

24 publications found

Variant links:

Genes affected

VEGFB (HGNC:12681): (vascular endothelial growth factor B) This gene encodes a member of the PDGF (platelet-derived growth factor)/VEGF (vascular endothelial growth factor) family. The VEGF family members regulate the formation of blood vessels and are involved in endothelial cell physiology. This member is a ligand for VEGFR-1 (vascular endothelial growth factor receptor 1) and NRP-1 (neuropilin-1). Studies in mice showed that this gene was co-expressed with nuclear-encoded mitochondrial genes and the encoded protein specifically controlled endothelial uptake of fatty acids. Alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Sep 2011]

VEGFB links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17276984).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003377.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFB	NM_003377.5	MANE Select	c.408C>G	p.Asp136Glu	missense splice_region	Exon 5 of 7	NP_003368.1	Q7LAP4
	VEGFB	NM_001243733.2		c.408C>G	p.Asp136Glu	missense splice_region	Exon 5 of 7	NP_001230662.1	P49765-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VEGFB	ENST00000309422.7	TSL:1 MANE Select	c.408C>G	p.Asp136Glu	missense splice_region	Exon 5 of 7	ENSP00000311127.2	P49765-1
VEGFB	ENST00000426086.3	TSL:1	c.408C>G	p.Asp136Glu	missense splice_region	Exon 5 of 7	ENSP00000401550.2	P49765-2
VEGFB	ENST00000970134.1		c.459C>G	p.Asp153Glu	missense splice_region	Exon 5 of 7	ENSP00000640193.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000419

AC:

AN:

238434

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000560

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

1733

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

-0.068

Eigen_PC

Benign

0.036

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.38

M_CAP

Benign

0.0043

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

1.4

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.58

REVEL

Benign

0.13

Sift

Benign

0.70

Sift4G

Benign

0.35

Polyphen

0.64

Vest4

0.46

MutPred

0.14

Gain of MoRF binding (P = 0.1219)

MVP

0.55

MPC

0.070

ClinPred

0.34

GERP RS

4.5

PromoterAI

-0.0037

Neutral

(source)

Varity_R

0.074

gMVP

0.17

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.019

dbscSNV1_RF

Benign

0.070

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over