11-64235995-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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. 14/20 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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.42

Publications

6 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:

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 (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 VariationId is 2641909.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 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 GnomAdExome4. There are 1308 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 gene

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.286C>G	p.Gln96Glu	missense	Exon 3 of 7	NP_003368.1	Q7LAP4
	VEGFB	NM_001243733.2		c.286C>G	p.Gln96Glu	missense	Exon 3 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.286C>G	p.Gln96Glu	missense	Exon 3 of 7	ENSP00000311127.2	P49765-1
VEGFB	ENST00000426086.3	TSL:1	c.286C>G	p.Gln96Glu	missense	Exon 3 of 7	ENSP00000401550.2	P49765-2
VEGFB	ENST00000970134.1		c.337C>G	p.Gln113Glu	missense	Exon 3 of 7	ENSP00000640193.1

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

318

AN:

152056

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00304

AC:

655

AN:

215120

AF XY:

0.00295

show subpopulations

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 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.:

Cov.:

AF XY:

0.00183

AC XY:

1308

AN XY:

716696

show subpopulations

African (AFR)

AF:

0.00181

AC:

AN:

33084

American (AMR)

AF:

0.00203

AC:

AN:

41394

Ashkenazi Jewish (ASJ)

AF:

0.0379

AC:

975

AN:

25732

East Asian (EAS)

AF:

0.0000259

AC:

AN:

38670

South Asian (SAS)

AF:

0.000189

AC:

AN:

84674

European-Finnish (FIN)

AF:

0.0000196

AC:

AN:

50916

Middle Eastern (MID)

AF:

0.0203

AC:

114

AN:

5622

European-Non Finnish (NFE)

AF:

0.000994

AC:

1097

AN:

1103508

Other (OTH)

AF:

0.00502

AC:

300

AN:

59702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

147

293

440

586

733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.00210

AC:

319

AN:

152174

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

150

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41522

American (AMR)

AF:

0.00405

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0366

AC:

127

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000831

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00138

AC:

AN:

68006

Other (OTH)

AF:

0.00475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00625

Hom.:

Bravo

AF:

0.00255

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00226

AC:

273

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

Eigen

Benign

-0.017

Eigen_PC

Benign

0.094

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

PhyloP100

2.4

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.30

REVEL

Benign

0.16

Sift

Uncertain

0.029

Sift4G

Uncertain

0.030

Polyphen

0.60

Vest4

0.29

MVP

0.28

MPC

0.069

ClinPred

0.017

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.33

Mutation Taster

=97/3

polymorphism

(source)

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

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