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.

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.812-33G>A		intron	N/A	NP_005420.1	P49767
	HAFML	NR_183975.1		n.182+17844C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.812-33G>A	intron	N/A	ENSP00000480043.1	P49767
HAFML	ENST00000504017.6	TSL:2	n.243+7803C>T	intron	N/A
HAFML	ENST00000509194.2	TSL:3	n.155+17844C>T	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over