11-64235995-C-G

Position:

• chr11-64235995-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003377.5(VEGFB):​c.286C>G​(p.Gln96Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,595,476 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (19 hom.)
• Consequence: VEGFB NM_003377.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.42

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005187243).
• BP6: Variant 11-64235995-C-G is Benign according to our data. Variant chr11-64235995-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2641909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00183 (2648/1443302) while in subpopulation MID AF= 0.0203 (114/5622). AF 95% confidence interval is 0.0173. There are 19 homozygotes in gnomad4_exome. There are 1308 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEGFB	NM_003377.5	c.286C>G	p.Gln96Glu	missense_variant	3/7	ENST00000309422.7	NP_003368.1
VEGFB	NM_001243733.2	c.286C>G	p.Gln96Glu	missense_variant	3/7		NP_001230662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFB	ENST00000309422.7	c.286C>G	p.Gln96Glu	missense_variant	3/7	1	NM_003377.5	ENSP00000311127
VEGFB	ENST00000426086.3	c.286C>G	p.Gln96Glu	missense_variant	3/7	1		ENSP00000401550	P1

Frequencies

GnomAD3 genomes AF: 0.00209 AC: 318 AN: 152056 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.00480

GnomAD3 exomes AF: 0.00304 AC: 655 AN: 215120 Hom.: 9 AF XY: 0.00295 AC XY: 345 AN XY: 116958

Gnomad AFR exome AF: 0.000224

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.0393

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000141

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00198

Gnomad OTH exome AF: 0.00607

GnomAD4 exome AF: 0.00183 AC: 2648 AN: 1443302 Hom.: 19 Cov.: 32 AF XY: 0.00183 AC XY: 1308 AN XY: 716696

Gnomad4 AFR exome AF: 0.00181

Gnomad4 AMR exome AF: 0.00203

Gnomad4 ASJ exome AF: 0.0379

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.000189

Gnomad4 FIN exome AF: 0.0000196

Gnomad4 NFE exome AF: 0.000994

Gnomad4 OTH exome AF: 0.00502

GnomAD4 genome AF: 0.00210 AC: 319 AN: 152174 Hom.: 5 Cov.: 32 AF XY: 0.00202 AC XY: 150 AN XY: 74386

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.00625 Hom.: 3

Bravo AF: 0.00255

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000683 AC: 3

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00226 AC: 273

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

VEGFB: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;.
Eigen	Benign	-0.017
Eigen_PC	Benign	0.094
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.76	T;T
MetaRNN	Benign	0.0052	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	0.65	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.30	N;N
REVEL	Benign	0.16
Sift	Uncertain	0.029	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.60	P;B
Vest4		0.29
MVP		0.28
MPC		0.069
ClinPred		0.017	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs111555072; hg19: chr11-64003467;