rs17697419

Positions:

• chr4-176687012-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005429.5(VEGFC):​c.1145+175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 152,126 control chromosomes in the GnomAD database, including 593 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 0.083 (593 hom., cov: 32)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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]

ENSG00000248388 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEGFC	NM_005429.5	c.1145+175C>T		intron_variant		ENST00000618562.2	NP_005420.1
HAFML	NR_183975.1	n.182+17303G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2	c.1145+175C>T		intron_variant		1	NM_005429.5	ENSP00000480043.1
ENSG00000248388	ENST00000504017.5	n.140+7262G>A		intron_variant		2
ENSG00000248388	ENST00000509194.1	n.89+17303G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0834 AC: 12676 AN: 152008 Hom.: 592 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0794

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0798

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

GnomAD4 genome AF: 0.0834 AC: 12685 AN: 152126 Hom.: 593 Cov.: 32 AF XY: 0.0800 AC XY: 5944 AN XY: 74344

Gnomad4 AFR AF: 0.0723

Gnomad4 AMR AF: 0.0611

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.000775

Gnomad4 SAS AF: 0.0305

Gnomad4 FIN AF: 0.0794

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0790

Alfa AF: 0.0997 Hom.: 96

Bravo AF: 0.0823

Asia WGS AF: 0.0200 AC: 71 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.2
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs17697419; hg19: chr4-177608166;