dbSNP rs6632528: VEGFD:c.-330A>G (chrX-15384276-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004469.5(VEGFD):c.-330A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 175,428 control chromosomes in the GnomAD database, including 6,122 homozygotes. There are 14,063 hemizygotes in GnomAD. 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 0.31 ( 4496 hom., 10375 hem., cov: 23)

Exomes 𝑓: 0.25 ( 1626 hom. 3688 hem. )

Consequence

VEGFD
NM_004469.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.122

Publications

8 publications found

Variant links:

Genes affected

VEGFD (HGNC:3708): (vascular endothelial growth factor D) The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family and is active in angiogenesis, lymphangiogenesis, and endothelial cell growth. This secreted protein undergoes a complex proteolytic maturation, generating multiple processed forms which bind and activate VEGFR-2 and VEGFR-3 receptors. This protein is structurally and functionally similar to vascular endothelial growth factor C. Read-through transcription has been observed between this locus and the upstream PIR (GeneID 8544) locus. [provided by RefSeq, Feb 2011]

VEGFD links:

PIR-FIGF (HGNC:):

PIR-FIGF links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEGFD	NM_004469.5 link	c.-330A>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000297904.4	NP_004460.1
PIR-FIGF	NR_037859.2 link	n.1065+5909A>G		intron_variant	Intron 9 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEGFD	ENST00000297904.4 link	c.-330A>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_004469.5	ENSP00000297904.3

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

34713

AN:

111633

Hom.:

4493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.490

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.298

GnomAD4 exome

AF:

0.254

AC:

16160

AN:

63742

Hom.:

1626

Cov.:

AF XY:

0.316

AC XY:

3688

AN XY:

11658

show subpopulations

African (AFR)

AF:

0.497

AC:

770

AN:

1549

American (AMR)

AF:

0.200

AC:

540

AN:

2703

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

324

AN:

1624

East Asian (EAS)

AF:

0.383

AC:

1020

AN:

2661

South Asian (SAS)

AF:

0.414

AC:

2276

AN:

5500

European-Finnish (FIN)

AF:

0.243

AC:

828

AN:

3403

Middle Eastern (MID)

AF:

0.280

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.223

AC:

9420

AN:

42314

Other (OTH)

AF:

0.244

AC:

917

AN:

3756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

437

874

1311

1748

2185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.311

AC:

34761

AN:

111686

Hom.:

4496

Cov.:

AF XY:

0.306

AC XY:

10375

AN XY:

33910

show subpopulations

African (AFR)

AF:

0.491

AC:

15070

AN:

30683

American (AMR)

AF:

0.226

AC:

2394

AN:

10608

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

509

AN:

2645

East Asian (EAS)

AF:

0.401

AC:

1419

AN:

3536

South Asian (SAS)

AF:

0.426

AC:

1154

AN:

2709

European-Finnish (FIN)

AF:

0.240

AC:

1441

AN:

6012

Middle Eastern (MID)

AF:

0.284

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.229

AC:

12166

AN:

53083

Other (OTH)

AF:

0.297

AC:

449

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

825

1650

2474

3299

4124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.250

Hom.:

20197

Bravo

AF:

0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.5

(source)

DANN

Benign

0.56

PhyloP100

-0.12

PromoterAI

0.053

Neutral

(source)

Mutation Taster

=300/0

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