chr4-176689877-G-T

Variant names:

• chr4-176689877-G-T
• rs3775203
• NM_005429.5:c.705-1950C>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.705-1950C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,900 control chromosomes in the GnomAD database, including 12,095 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 0.39 (12095 hom., cov: 32)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEGFC	NM_005429.5	c.705-1950C>A		intron_variant	Intron 4 of 6	ENST00000618562.2	NP_005420.1
HAFML	NR_183975.1	n.183-16026G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2	c.705-1950C>A		intron_variant	Intron 4 of 6	1	NM_005429.5	ENSP00000480043.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58656 AN: 151782 Hom.: 12087 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.386 AC: 58669 AN: 151900 Hom.: 12095 Cov.: 32 AF XY: 0.385 AC XY: 28577 AN XY: 74210

African (AFR) AF: 0.235 AC: 9752 AN: 41452

American (AMR) AF: 0.405 AC: 6190 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1490 AN: 3466

East Asian (EAS) AF: 0.545 AC: 2810 AN: 5158

South Asian (SAS) AF: 0.415 AC: 1993 AN: 4804

European-Finnish (FIN) AF: 0.400 AC: 4207 AN: 10526

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30904 AN: 67916

Other (OTH) AF: 0.379 AC: 799 AN: 2110

Alfa AF: 0.422 Hom.: 23810

Bravo AF: 0.379

Asia WGS AF: 0.448 AC: 1558 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.35
DANN	Benign	0.45
PhyloP100		-0.98
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: rs3775203; hg19: chr4-177611031;