Genetic Variant VEGFC:c.705-1803A>C (chr4-176689730-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005429.5(VEGFC):c.705-1803A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,040 control chromosomes in the GnomAD database, including 12,920 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 0.38 ( 12920 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VEGFC
NM_005429.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.145

Publications

27 publications found

Variant links:

Genes affected

VEGFC (HGNC:12682): (vascular endothelial growth factor C) The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family. The encoded protein promotes angiogenesis and endothelial cell growth, and can also affect the permeability of blood vessels. The proprotein is further cleaved into a fully processed form that can bind and activate VEGFR-2 and VEGFR-3 receptors. [provided by RefSeq, Apr 2014]

VEGFC links:

HAFML (HGNC:56694): (HuR (ELAVL1) associated fibroblast migratory lncRNA)

HAFML links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005429.5. 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
	VEGFC	NM_005429.5	MANE Select	c.705-1803A>C		intron	N/A	NP_005420.1	P49767
	HAFML	NR_183975.1		n.183-16173T>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.705-1803A>C	intron	N/A	ENSP00000480043.1	P49767
HAFML	ENST00000504017.6	TSL:2	n.243+9980T>G	intron	N/A
VEGFC	ENST00000507638.1	TSL:3	n.404-75A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57706

AN:

151922

Hom.:

12921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.505

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.398

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.380

AC:

57704

AN:

152040

Hom.:

12920

Cov.:

AF XY:

0.377

AC XY:

28033

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.135

AC:

5615

AN:

41522

American (AMR)

AF:

0.346

AC:

5280

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.405

AC:

1404

AN:

3470

East Asian (EAS)

AF:

0.506

AC:

2612

AN:

5164

South Asian (SAS)

AF:

0.486

AC:

2334

AN:

4800

European-Finnish (FIN)

AF:

0.436

AC:

4597

AN:

10546

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.507

AC:

34457

AN:

67962

Other (OTH)

AF:

0.398

AC:

838

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1636

3272

4908

6544

8180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.451

Hom.:

23838

Bravo

AF:

0.363

Asia WGS

AF:

0.449

AC:

1563

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.62

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over