11-64236371-G-T

Variant names:

• chr11-64236371-G-T
• rs11603042
• NM_003377.5:c.374+44G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003377.5(VEGFB):​c.374+44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,591,162 control chromosomes in the GnomAD database, including 89,761 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6646 hom., cov: 31)
  • Exomes 𝑓: 0.34 (83115 hom.)
• Consequence: VEGFB NM_003377.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

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.374+44G>T		intron	N/A	NP_003368.1	Q7LAP4
	VEGFB	NM_001243733.2		c.374+44G>T		intron	N/A	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.374+44G>T		intron	N/A	ENSP00000311127.2	P49765-1
	VEGFB	ENST00000426086.3	TSL:1	c.374+44G>T		intron	N/A	ENSP00000401550.2	P49765-2
	VEGFB	ENST00000970134.1		c.425+44G>T		intron	N/A	ENSP00000640193.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42960 AN: 151860 Hom.: 6642 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.301

GnomAD2 exomes AF: 0.306 AC: 74868 AN: 244836 AF XY: 0.303

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.271

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.335 AC: 482629 AN: 1439186 Hom.: 83115 Cov.: 26 AF XY: 0.331 AC XY: 237258 AN XY: 716912

African (AFR) AF: 0.146 AC: 4809 AN: 32952

American (AMR) AF: 0.399 AC: 17738 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 6229 AN: 25912

East Asian (EAS) AF: 0.290 AC: 11438 AN: 39496

South Asian (SAS) AF: 0.186 AC: 15925 AN: 85628

European-Finnish (FIN) AF: 0.316 AC: 16286 AN: 51542

Middle Eastern (MID) AF: 0.249 AC: 1420 AN: 5714

European-Non Finnish (NFE) AF: 0.356 AC: 389642 AN: 1093760

Other (OTH) AF: 0.321 AC: 19142 AN: 59702

GnomAD4 genome AF: 0.283 AC: 42983 AN: 151976 Hom.: 6646 Cov.: 31 AF XY: 0.282 AC XY: 20933 AN XY: 74302

African (AFR) AF: 0.155 AC: 6448 AN: 41486

American (AMR) AF: 0.372 AC: 5685 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 838 AN: 3466

East Asian (EAS) AF: 0.272 AC: 1406 AN: 5162

South Asian (SAS) AF: 0.179 AC: 862 AN: 4824

European-Finnish (FIN) AF: 0.303 AC: 3200 AN: 10558

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23580 AN: 67902

Other (OTH) AF: 0.305 AC: 640 AN: 2100

Alfa AF: 0.319 Hom.: 8882

Bravo AF: 0.285

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs11603042; hg19: chr11-64003843; COSMIC: COSV58535453; COSMIC: COSV58535453;