4-176689877-G-T

Position:

• chr4-176689877-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• 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/exons	MANE	Protein	UniProt
VEGFC	NM_005429.5	c.705-1950C>A		intron_variant		ENST00000618562.2	NP_005420.1
HAFML	NR_183975.1	n.183-16026G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2	c.705-1950C>A		intron_variant		1	NM_005429.5	ENSP00000480043	P1
HAFML	ENST00000509194.1	n.90-16026G>T		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+10127G>T		intron_variant, non_coding_transcript_variant		2
VEGFC	ENST00000507638.1	n.404-222C>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.379

Alfa AF: 0.380 Hom.: 2548

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

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: rs3775203; hg19: chr4-177611031;