4-176706798-C-T

Variant names:

• chr4-176706798-C-T
• rs1485765
• NM_005429.5:c.704+4701G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005429.5(VEGFC):​c.704+4701G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,066 control chromosomes in the GnomAD database, including 44,374 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 0.72 (44374 hom., cov: 31)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76
• Publications: 6 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	NM_005429.5	MANE Select	c.704+4701G>A		intron	N/A	NP_005420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.704+4701G>A		intron	N/A	ENSP00000480043.1
	VEGFC	ENST00000507638.1	TSL:3	n.403+4701G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109862 AN: 151948 Hom.: 44376 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.723 AC: 109884 AN: 152066 Hom.: 44374 Cov.: 31 AF XY: 0.730 AC XY: 54250 AN XY: 74352

African (AFR) AF: 0.330 AC: 13660 AN: 41410

American (AMR) AF: 0.754 AC: 11524 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 3086 AN: 3472

East Asian (EAS) AF: 0.940 AC: 4858 AN: 5168

South Asian (SAS) AF: 0.876 AC: 4221 AN: 4818

European-Finnish (FIN) AF: 0.911 AC: 9647 AN: 10592

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60218 AN: 68018

Other (OTH) AF: 0.776 AC: 1636 AN: 2108

Alfa AF: 0.769 Hom.: 7037

Bravo AF: 0.693

Asia WGS AF: 0.863 AC: 3003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.63
PhyloP100		-2.8
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: rs1485765; hg19: chr4-177627952;