rs6418686

Positions:

• chrX-15369884-T-C
• chrX-15369884-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004469.5(VEGFD):​c.91-6565A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 110,930 control chromosomes in the GnomAD database, including 9,469 homozygotes. There are 13,748 hemizygotes in GnomAD. 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 0.43 (9469 hom., 13748 hem., cov: 23)
• Consequence: VEGFD NM_004469.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975

Genes affected

VEGFD (HGNC:3708): (vascular endothelial growth factor D) The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family and is active in angiogenesis, lymphangiogenesis, and endothelial cell growth. This secreted protein undergoes a complex proteolytic maturation, generating multiple processed forms which bind and activate VEGFR-2 and VEGFR-3 receptors. This protein is structurally and functionally similar to vascular endothelial growth factor C. Read-through transcription has been observed between this locus and the upstream PIR (GeneID 8544) locus. [provided by RefSeq, Feb 2011]

PIR-FIGF (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEGFD	NM_004469.5	c.91-6565A>G		intron_variant		ENST00000297904.4	NP_004460.1
PIR-FIGF	NR_037859.2	n.1066-6565A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFD	ENST00000297904.4	c.91-6565A>G		intron_variant		1	NM_004469.5	ENSP00000297904	P1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 47568 AN: 110885 Hom.: 9463 Cov.: 23 AF XY: 0.414 AC XY: 13706 AN XY: 33113

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.429 AC: 47614 AN: 110930 Hom.: 9469 Cov.: 23 AF XY: 0.414 AC XY: 13748 AN XY: 33168

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.420

Alfa AF: 0.365 Hom.: 4264

Bravo AF: 0.446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.30
DANN	Benign	0.66

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: rs6418686; hg19: chrX-15388006;