4-176690243-G-A

Variant names:

• chr4-176690243-G-A
• rs11947611
• NM_005429.5:c.705-2316C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005429.5(VEGFC):​c.705-2316C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,678 control chromosomes in the GnomAD database, including 19,109 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 0.50 (19109 hom., cov: 32)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 13 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	NM_005429.5	MANE Select	c.705-2316C>T		intron	N/A	NP_005420.1
	HAFML	NR_183975.1		n.183-15660G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.705-2316C>T		intron	N/A	ENSP00000480043.1
	HAFML	ENST00000504017.6	TSL:2	n.243+10493G>A		intron	N/A
	VEGFC	ENST00000507638.1	TSL:3	n.404-588C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75964 AN: 151568 Hom.: 19099 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.501 AC: 76006 AN: 151678 Hom.: 19109 Cov.: 32 AF XY: 0.497 AC XY: 36865 AN XY: 74124

African (AFR) AF: 0.538 AC: 22262 AN: 41388

American (AMR) AF: 0.462 AC: 7047 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1607 AN: 3462

East Asian (EAS) AF: 0.607 AC: 3140 AN: 5174

South Asian (SAS) AF: 0.489 AC: 2352 AN: 4808

European-Finnish (FIN) AF: 0.437 AC: 4555 AN: 10412

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.493 AC: 33462 AN: 67876

Other (OTH) AF: 0.486 AC: 1023 AN: 2104

Alfa AF: 0.494 Hom.: 9272

Bravo AF: 0.503

Asia WGS AF: 0.506 AC: 1755 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.9
DANN	Benign	0.37
PhyloP100		1.1
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: rs11947611; hg19: chr4-177611397;