rs2333496

Variant names:

• chr4-176688455-C-T
• rs2333496
• NM_005429.5:c.705-528G>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.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
• Publications: 7 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005429.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	NM_005429.5	MANE Select	c.705-528G>A		intron	N/A	NP_005420.1	P49767
	HAFML	NR_183975.1		n.183-17448C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.705-528G>A		intron	N/A	ENSP00000480043.1	P49767
	HAFML	ENST00000504017.6	TSL:2	n.243+8705C>T		intron	N/A
	HAFML	ENST00000509194.2	TSL:3	n.156-17448C>T		intron	N/A

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

African (AFR) AF: 0.170 AC: 7068 AN: 41476

American (AMR) AF: 0.565 AC: 8629 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2341 AN: 3472

East Asian (EAS) AF: 0.707 AC: 3652 AN: 5164

South Asian (SAS) AF: 0.734 AC: 3531 AN: 4812

European-Finnish (FIN) AF: 0.751 AC: 7938 AN: 10566

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.695 AC: 47227 AN: 67948

Other (OTH) AF: 0.565 AC: 1195 AN: 2114

Alfa AF: 0.529 Hom.: 3733

Bravo AF: 0.510

Asia WGS AF: 0.685 AC: 2380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.63
PhyloP100		-0.23
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: rs2333496; hg19: chr4-177609609;