11-64236001-C-G

Variant names:

• chr11-64236001-C-G
• rs762404988
• NM_003377.5:c.292C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003377.5(VEGFB):​c.292C>G​(p.Arg98Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,758 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R98W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: VEGFB NM_003377.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.759
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.292C>G	p.Arg98Gly	missense	Exon 3 of 7	NP_003368.1	Q7LAP4
	VEGFB	NM_001243733.2		c.292C>G	p.Arg98Gly	missense	Exon 3 of 7	NP_001230662.1	P49765-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFB	ENST00000309422.7	TSL:1 MANE Select	c.292C>G	p.Arg98Gly	missense	Exon 3 of 7	ENSP00000311127.2	P49765-1
	VEGFB	ENST00000426086.3	TSL:1	c.292C>G	p.Arg98Gly	missense	Exon 3 of 7	ENSP00000401550.2	P49765-2
	VEGFB	ENST00000970134.1		c.343C>G	p.Arg115Gly	missense	Exon 3 of 7	ENSP00000640193.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438758 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 713978

African (AFR) AF: 0.00 AC: 0 AN: 32976

American (AMR) AF: 0.00 AC: 0 AN: 40624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25664

East Asian (EAS) AF: 0.00 AC: 0 AN: 38384

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101134

Other (OTH) AF: 0.00 AC: 0 AN: 59532

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0046	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.76
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.22
Sift	Benign	0.078	T
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.53		Loss of MoRF binding (P = 0.0207)
MVP		0.61
MPC		0.14
ClinPred		0.94	D
GERP RS		4.9
Varity_R		0.66
gMVP		0.53
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs762404988; hg19: chr11-64003473;