Variant 4-176687553-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
VEGFC	NM_005429.5 linkuse as main transcript	c.812-33G>A		intron_variant		ENST00000618562.2	NP_005420.1
HAFML	NR_183975.1 linkuse as main transcript	n.182+17844C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
VEGFC	ENST00000618562.2 linkuse as main transcript	c.812-33G>A	intron_variant	1	NM_005429.5	ENSP00000480043	P1
HAFML	ENST00000509194.1 linkuse as main transcript	n.89+17844C>T	intron_variant, non_coding_transcript_variant	3
HAFML	ENST00000504017.5 linkuse as main transcript	n.140+7803C>T	intron_variant, non_coding_transcript_variant	2

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

GnomAD3 exomes

AF:

0.240

AC:

32160

AN:

134274

Hom.:

4006

AF XY:

0.233

AC XY:

16638

AN XY:

71442

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 SAS exome

AF:

0.227

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

Gnomad4 AFR exome

AF:

0.328

Gnomad4 AMR exome

AF:

0.352

Gnomad4 ASJ exome

AF:

0.193

Gnomad4 EAS exome

AF:

0.297

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.191

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.247

AC:

37498

AN:

152056

Hom.:

5093

Cov.:

AF XY:

0.244

AC XY:

18124

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.317

Gnomad4 ASJ

AF:

0.183

Gnomad4 EAS

AF:

0.292

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.255

Alfa

AF:

0.210

Hom.:

5018

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

DANN

Benign

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over