Variant 11-64237220-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003377.5(VEGFB):c.408C>T(p.Asp136=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,554,184 control chromosomes in the GnomAD database, including 65,282 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4045 hom., cov: 28)

Exomes 𝑓: 0.28 ( 61237 hom. )

Consequence

VEGFB
NM_003377.5 splice_region, synonymous

Scores

Splicing: ADA: 0.4939

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.41

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 Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 11-64237220-C-T is Benign according to our data. Variant chr11-64237220-C-T is described in ClinVar as [Benign]. Clinvar id is 769376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-64237220-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEGFB	NM_003377.5 linkuse as main transcript	c.408C>T	p.Asp136=	splice_region_variant, synonymous_variant	5/7	ENST00000309422.7	NP_003368.1
VEGFB	NM_001243733.2 linkuse as main transcript	c.408C>T	p.Asp136=	splice_region_variant, synonymous_variant	5/7		NP_001230662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFB	ENST00000309422.7 linkuse as main transcript	c.408C>T	p.Asp136=	splice_region_variant, synonymous_variant	5/7	1	NM_003377.5	ENSP00000311127		P49765-1
VEGFB	ENST00000426086.3 linkuse as main transcript	c.408C>T	p.Asp136=	splice_region_variant, synonymous_variant	5/7	1		ENSP00000401550	P1	P49765-2
VEGFB	ENST00000543462.1 linkuse as main transcript	n.94C>T		splice_region_variant, non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

29665

AN:

147180

Hom.:

4047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0503

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.230

AC:

54906

AN:

238434

Hom.:

8718

AF XY:

0.245

AC XY:

31488

AN XY:

128770

show subpopulations

Gnomad AFR exome

AF:

0.0436

Gnomad AMR exome

AF:

0.0956

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.258

Gnomad NFE exome

AF:

0.297

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

AF:

0.276

AC:

388000

AN:

1406888

Hom.:

61237

Cov.:

AF XY:

0.279

AC XY:

194764

AN XY:

698190

show subpopulations

Gnomad4 AFR exome

AF:

0.0400

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.226

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.294

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.253

GnomAD4 genome

AF:

0.201

AC:

29652

AN:

147296

Hom.:

4045

Cov.:

AF XY:

0.199

AC XY:

14266

AN XY:

71662

show subpopulations

Gnomad4 AFR

AF:

0.0503

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.227

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.286

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.239

Hom.:

1733

Bravo

AF:

0.196

Asia WGS

AF:

0.177

AC:

616

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.49

dbscSNV1_RF

Benign

0.40

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

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