rs7664413

Positions:

• chr4-176687553-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.812-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,501,854 control chromosomes in the GnomAD database, including 33,669 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 0.25 (5093 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28576 hom.)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEGFC	NM_005429.5	c.812-33G>A		intron_variant		ENST00000618562.2	NP_005420.1
HAFML	NR_183975.1	n.182+17844C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2	c.812-33G>A		intron_variant		1	NM_005429.5	ENSP00000480043	P1
HAFML	ENST00000509194.1	n.89+17844C>T		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+7803C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37453 AN: 151938 Hom.: 5079 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.252

GnomAD3 exomes AF: 0.240 AC: 32160 AN: 134274 Hom.: 4006 AF XY: 0.233 AC XY: 16638 AN XY: 71442

Gnomad AFR exome AF: 0.330

Gnomad AMR exome AF: 0.373

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.298

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.198

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.202 AC: 272439 AN: 1349798 Hom.: 28576 Cov.: 28 AF XY: 0.202 AC XY: 133704 AN XY: 662174

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.225

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.213

GnomAD4 genome AF: 0.247 AC: 37498 AN: 152056 Hom.: 5093 Cov.: 32 AF XY: 0.244 AC XY: 18124 AN XY: 74344

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.255

Alfa AF: 0.210 Hom.: 5018

Bravo AF: 0.263

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.79

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: rs7664413; hg19: chr4-177608707;