chr4-176702723-C-G

Variant names:

• chr4-176702723-C-G
• rs3775194
• NM_005429.5:c.704+8776G>C

Variant summary

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

The NM_005429.5(VEGFC):​c.704+8776G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,904 control chromosomes in the GnomAD database, including 20,984 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 0.49 (20984 hom., cov: 32)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 12 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 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.704+8776G>C		intron	N/A	NP_005420.1	P49767
	HAFML	NR_183975.1		n.183-3180C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.704+8776G>C		intron	N/A	ENSP00000480043.1	P49767
	HAFML	ENST00000504017.6	TSL:2	n.244-3180C>G		intron	N/A
	VEGFC	ENST00000507638.1	TSL:3	n.403+8776G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73678 AN: 151786 Hom.: 20985 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.485 AC: 73680 AN: 151904 Hom.: 20984 Cov.: 32 AF XY: 0.487 AC XY: 36141 AN XY: 74216

African (AFR) AF: 0.178 AC: 7389 AN: 41500

American (AMR) AF: 0.490 AC: 7466 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2376 AN: 3466

East Asian (EAS) AF: 0.869 AC: 4489 AN: 5164

South Asian (SAS) AF: 0.603 AC: 2905 AN: 4818

European-Finnish (FIN) AF: 0.575 AC: 6057 AN: 10542

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41140 AN: 67852

Other (OTH) AF: 0.552 AC: 1163 AN: 2108

Alfa AF: 0.398 Hom.: 1255

Bravo AF: 0.469

Asia WGS AF: 0.692 AC: 2404 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.53
PhyloP100		-0.15
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: rs3775194; hg19: chr4-177623877;