4-176732444-C-T

Variant names:

• chr4-176732444-C-T
• rs6838834
• NM_005429.5:c.148-2698G>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.148-2698G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 151,860 control chromosomes in the GnomAD database, including 226 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 0.036 (226 hom., cov: 31)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.0964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEGFC	NM_005429.5	c.148-2698G>A		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.148-2698G>A		intron_variant	Intron 1 of 6	1	NM_005429.5	ENSP00000480043.1

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5376 AN: 151742 Hom.: 220 Cov.: 31

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.00739

Gnomad OTH AF: 0.0451

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

GnomAD4 genome AF: 0.0356 AC: 5408 AN: 151860 Hom.: 226 Cov.: 31 AF XY: 0.0344 AC XY: 2555 AN XY: 74222

African (AFR) AF: 0.0990 AC: 4100 AN: 41432

American (AMR) AF: 0.0308 AC: 469 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 153 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00312 AC: 15 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.00739 AC: 502 AN: 67904

Other (OTH) AF: 0.0446 AC: 94 AN: 2108

Alfa AF: 0.0162 Hom.: 53

Bravo AF: 0.0419

Asia WGS AF: 0.0160 AC: 56 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.84
DANN	Benign	0.26
PhyloP100		-1.2
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: rs6838834; hg19: chr4-177653598;