chr4-176713368-A-G

Position:

• chr4-176713368-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005429.5(VEGFC):​c.553-1718T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,050 control chromosomes in the GnomAD database, including 43,513 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 0.70 (43513 hom., cov: 32)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEGFC	NM_005429.5	c.553-1718T>C		intron_variant		ENST00000618562.2	NP_005420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2	c.553-1718T>C		intron_variant		1	NM_005429.5	ENSP00000480043.1
VEGFC	ENST00000507638.1	n.252-1718T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106910 AN: 151934 Hom.: 43516 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.758

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.703 AC: 106919 AN: 152050 Hom.: 43513 Cov.: 32 AF XY: 0.711 AC XY: 52883 AN XY: 74338

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.926

Gnomad4 NFE AF: 0.885

Gnomad4 OTH AF: 0.761

Alfa AF: 0.856 Hom.: 55242

Bravo AF: 0.670

Asia WGS AF: 0.857 AC: 2963 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.5
DANN	Benign	0.88

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

Other links and lift over

dbSNP: rs1564922; hg19: chr4-177634522;