rs4557213

Variant names:

• chr4-176767979-G-A
• rs4557213
• NM_005429.5:c.147+24186C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-176767979-G-A
• chr4-176767979-G-C
• chr4-176767979-G-T

Variant summary

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

The NM_005429.5(VEGFC):​c.147+24186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,014 control chromosomes in the GnomAD database, including 53,370 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 0.83 (53370 hom., cov: 30)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 7 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEGFC	NM_005429.5	c.147+24186C>T		intron_variant	Intron 1 of 6	ENST00000618562.2	NP_005420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2	c.147+24186C>T		intron_variant	Intron 1 of 6	1	NM_005429.5	ENSP00000480043.1

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125421 AN: 151896 Hom.: 53346 Cov.: 30

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.881

Gnomad AMR AF: 0.895

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.904

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.826 AC: 125493 AN: 152014 Hom.: 53370 Cov.: 30 AF XY: 0.832 AC XY: 61872 AN XY: 74328

African (AFR) AF: 0.595 AC: 24636 AN: 41388

American (AMR) AF: 0.895 AC: 13678 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 3191 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5126 AN: 5130

South Asian (SAS) AF: 0.975 AC: 4702 AN: 4824

European-Finnish (FIN) AF: 0.933 AC: 9890 AN: 10602

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.904 AC: 61452 AN: 68004

Other (OTH) AF: 0.840 AC: 1774 AN: 2112

Alfa AF: 0.874 Hom.: 161965

Bravo AF: 0.812

Asia WGS AF: 0.963 AC: 3349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.7
DANN	Benign	0.95
PhyloP100		-0.29
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: rs4557213; hg19: chr4-177689133;