4-176743719-T-C

Variant names:

• chr4-176743719-T-C
• rs1385737
• NM_005429.5:c.148-13973A>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.148-13973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 151,532 control chromosomes in the GnomAD database, including 43,619 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 0.71 (43619 hom., cov: 31)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEGFC	NM_005429.5	c.148-13973A>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.148-13973A>G		intron_variant	Intron 1 of 6	1	NM_005429.5	ENSP00000480043.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 106931 AN: 151434 Hom.: 43628 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.706 AC: 106931 AN: 151532 Hom.: 43619 Cov.: 31 AF XY: 0.714 AC XY: 52890 AN XY: 74042

African (AFR) AF: 0.261 AC: 10816 AN: 41394

American (AMR) AF: 0.770 AC: 11671 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3092 AN: 3468

East Asian (EAS) AF: 0.932 AC: 4784 AN: 5134

South Asian (SAS) AF: 0.875 AC: 4206 AN: 4808

European-Finnish (FIN) AF: 0.926 AC: 9666 AN: 10438

Middle Eastern (MID) AF: 0.793 AC: 230 AN: 290

European-Non Finnish (NFE) AF: 0.886 AC: 60062 AN: 67826

Other (OTH) AF: 0.762 AC: 1604 AN: 2106

Alfa AF: 0.790 Hom.: 14685

Bravo AF: 0.675

Asia WGS AF: 0.850 AC: 2941 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.68
PhyloP100		0.82
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: rs1385737; hg19: chr4-177664873;