chr4-176782151-T-C

Variant names:

• chr4-176782151-T-C
• rs2333526
• NM_005429.5:c.147+10014A>G

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+10014A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,304 control chromosomes in the GnomAD database, including 59,691 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 0.88 (59691 hom., cov: 35)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 5 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=-0.92).
• 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+10014A>G		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+10014A>G		intron_variant	Intron 1 of 6	1	NM_005429.5	ENSP00000480043.1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134336 AN: 152186 Hom.: 59658 Cov.: 35

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.977

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.883 AC: 134423 AN: 152304 Hom.: 59691 Cov.: 35 AF XY: 0.888 AC XY: 66108 AN XY: 74478

African (AFR) AF: 0.777 AC: 32259 AN: 41542

American (AMR) AF: 0.929 AC: 14215 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3316 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5178 AN: 5182

South Asian (SAS) AF: 0.977 AC: 4720 AN: 4830

European-Finnish (FIN) AF: 0.933 AC: 9914 AN: 10624

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61794 AN: 68032

Other (OTH) AF: 0.895 AC: 1893 AN: 2116

Alfa AF: 0.906 Hom.: 67187

Bravo AF: 0.878

Asia WGS AF: 0.980 AC: 3408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.27
PhyloP100		-1.4
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: rs2333526; hg19: chr4-177703305;