Variant chr11-64237214-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003377.5(VEGFB):c.402G>T(p.Lys134Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,608,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

VEGFB
NM_003377.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34750617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEGFB	NM_003377.5 linkuse as main transcript	c.402G>T	p.Lys134Asn	missense_variant	5/7	ENST00000309422.7
VEGFB	NM_001243733.2 linkuse as main transcript	c.402G>T	p.Lys134Asn	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEGFB	ENST00000309422.7 linkuse as main transcript	c.402G>T	p.Lys134Asn	missense_variant	5/7	1	NM_003377.5		P49765-1
VEGFB	ENST00000426086.3 linkuse as main transcript	c.402G>T	p.Lys134Asn	missense_variant	5/7	1		P1	P49765-2
VEGFB	ENST00000543462.1 linkuse as main transcript	n.88G>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458174

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725380

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150808

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73488

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000662

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.402G>T (p.K134N) alteration is located in exon 1 (coding exon 1) of the VEGFB gene. This alteration results from a G to T substitution at nucleotide position 402, causing the lysine (K) at amino acid position 134 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.53

N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.0

N;D

REVEL

Benign

0.25

Sift

Benign

0.051

T;D

Sift4G

Uncertain

0.031

D;T

Polyphen

0.68

P;P

Vest4

0.51

MutPred

0.30

Loss of methylation at K134 (P = 0.0051);Loss of methylation at K134 (P = 0.0051);

MVP

0.48

MPC

0.046

ClinPred

0.68

GERP RS

3.6

Varity_R

0.099

gMVP

0.24

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