rs2333496

Positions:

• chr4-176688455-C-T

Variant summary

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

The NM_005429.5(VEGFC):​c.705-528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,026 control chromosomes in the GnomAD database, including 26,614 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 0.54 (26614 hom., cov: 32)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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]

HAFML (HGNC:56694): (HuR (ELAVL1) associated fibroblast migratory lncRNA)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEGFC	NM_005429.5	c.705-528G>A		intron_variant		ENST00000618562.2
HAFML	NR_183975.1	n.183-17448C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEGFC	ENST00000618562.2	c.705-528G>A		intron_variant		1	NM_005429.5	P1
HAFML	ENST00000509194.1	n.90-17448C>T		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+8705C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82426 AN: 151908 Hom.: 26628 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.542 AC: 82404 AN: 152026 Hom.: 26614 Cov.: 32 AF XY: 0.553 AC XY: 41078 AN XY: 74302

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.565

Alfa AF: 0.542 Hom.: 3722

Bravo AF: 0.510

Asia WGS AF: 0.685 AC: 2380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.63

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: rs2333496; hg19: chr4-177609609;