dbSNP rs7664413: VEGFC:c.812-33G>A (chr4-176687553-C-T) – 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.812-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,501,854 control chromosomes in the GnomAD database, including 33,669 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 0.25 ( 5093 hom., cov: 32)

Exomes 𝑓: 0.20 ( 28576 hom. )

Consequence

VEGFC
NM_005429.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

Publications

33 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=-0.59).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEGFC	NM_005429.5 link	c.812-33G>A		intron_variant	Intron 5 of 6	ENST00000618562.2	NP_005420.1	P49767
HAFML	NR_183975.1 link	n.182+17844C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2 link	c.812-33G>A		intron_variant	Intron 5 of 6	1	NM_005429.5	ENSP00000480043.1		P49767

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37453

AN:

151938

Hom.:

5079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.0901

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.252

GnomAD2 exomes

AF:

0.240

AC:

32160

AN:

134274

AF XY:

0.233

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.373

Gnomad ASJ exome

AF:

0.207

Gnomad EAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.198

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.202

AC:

272439

AN:

1349798

Hom.:

28576

Cov.:

AF XY:

0.202

AC XY:

133704

AN XY:

662174

show subpopulations

African (AFR)

AF:

0.328

AC:

9699

AN:

29546

American (AMR)

AF:

0.352

AC:

8914

AN:

25318

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

3977

AN:

20618

East Asian (EAS)

AF:

0.297

AC:

11086

AN:

37322

South Asian (SAS)

AF:

0.225

AC:

15825

AN:

70186

European-Finnish (FIN)

AF:

0.177

AC:

8233

AN:

46394

Middle Eastern (MID)

AF:

0.184

AC:

874

AN:

4738

European-Non Finnish (NFE)

AF:

0.191

AC:

201971

AN:

1059926

Other (OTH)

AF:

0.213

AC:

11860

AN:

55750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

11212

22425

33637

44850

56062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7482

14964

22446

29928

37410

<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:

0.247

AC:

37498

AN:

152056

Hom.:

5093

Cov.:

AF XY:

0.244

AC XY:

18124

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.330

AC:

13691

AN:

41492

American (AMR)

AF:

0.317

AC:

4845

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

635

AN:

3466

East Asian (EAS)

AF:

0.292

AC:

1507

AN:

5158

South Asian (SAS)

AF:

0.226

AC:

1091

AN:

4824

European-Finnish (FIN)

AF:

0.169

AC:

1785

AN:

10578

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13268

AN:

67950

Other (OTH)

AF:

0.255

AC:

538

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1372

2744

4115

5487

6859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.218

Hom.:

12013

Bravo

AF:

0.263

Asia WGS

AF:

0.255

AC:

889

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

2.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over