rs17063612

chr4-176709876-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005429.5(VEGFC):c.704+1623A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 152,230 control chromosomes in the GnomAD database, including 24 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 0.0063 (24 hom., cov: 32)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00625 (952/152230) while in subpopulation EAS AF= 0.0536 (277/5168). AF 95% confidence interval is 0.0484. There are 24 homozygotes in gnomad4. There are 587 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 950 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEGFC	NM_005429.5	c.704+1623A>T		intron_variant		ENST00000618562.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEGFC	ENST00000618562.2	c.704+1623A>T		intron_variant		1	NM_005429.5	P1
VEGFC	ENST00000507638.1	n.403+1623A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00625 AC: 950 AN: 152112 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0537

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00525

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

GnomAD4 genome AF: 0.00625 AC: 952 AN: 152230 Hom.: 24 Cov.: 32 AF XY: 0.00789 AC XY: 587 AN XY: 74424

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.0375

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0536

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00169 Hom.: 1

Bravo AF: 0.00784

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.0
Dann	Benign	0.51

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: rs17063612; hg19: chr4-177631030;