NM_005429.5:c.553-1718T>C

Variant names:

• chr4-176713368-A-G
• rs1564922
• NM_005429.5:c.553-1718T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• lymphatic malformation 4

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• lymphatic malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

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.553-1718T>C		intron	N/A	NP_005420.1	P49767

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.553-1718T>C		intron	N/A	ENSP00000480043.1	P49767
	VEGFC	ENST00000507638.1	TSL:3	n.252-1718T>C		intron	N/A

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

African (AFR) AF: 0.260 AC: 10766 AN: 41476

American (AMR) AF: 0.746 AC: 11388 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3083 AN: 3470

East Asian (EAS) AF: 0.939 AC: 4860 AN: 5174

South Asian (SAS) AF: 0.876 AC: 4215 AN: 4810

European-Finnish (FIN) AF: 0.926 AC: 9807 AN: 10594

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.885 AC: 60168 AN: 67960

Other (OTH) AF: 0.761 AC: 1602 AN: 2104

Alfa AF: 0.794 Hom.: 80759

Bravo AF: 0.670

Asia WGS AF: 0.857 AC: 2963 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.5
DANN	Benign	0.88
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1564922; hg19: chr4-177634522;