rs17697515

Positions:

• chr4-176689270-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.705-1343G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 152,130 control chromosomes in the GnomAD database, including 272 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 0.051 (272 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEGFC	NM_005429.5	c.705-1343G>A		intron_variant		ENST00000618562.2	NP_005420.1
HAFML	NR_183975.1	n.183-16633C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2	c.705-1343G>A		intron_variant		1	NM_005429.5	ENSP00000480043	P1
HAFML	ENST00000509194.1	n.90-16633C>T		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+9520C>T		intron_variant, non_coding_transcript_variant		2
VEGFC	ENST00000507638.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0506 AC: 7689 AN: 152012 Hom.: 271 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0596

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0556

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0506 AC: 7691 AN: 152130 Hom.: 272 Cov.: 32 AF XY: 0.0487 AC XY: 3619 AN XY: 74346

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.0431

Gnomad4 ASJ AF: 0.0596

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0681

Gnomad4 NFE AF: 0.0780

Gnomad4 OTH AF: 0.0550

Alfa AF: 0.0699 Hom.: 114

Bravo AF: 0.0467

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17697515; hg19: chr4-177610424;