rs6632528

Positions:

• chrX-15384276-T-C

Variant summary

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

The NM_004469.5(VEGFD):​c.-330A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 175,428 control chromosomes in the GnomAD database, including 6,122 homozygotes. There are 14,063 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 0.31 (4496 hom., 10375 hem., cov: 23)
  • Exomes 𝑓: 0.25 (1626 hom. 3688 hem.)
• Consequence: VEGFD NM_004469.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEGFD	NM_004469.5	c.-330A>G		5_prime_UTR_variant	1/7	ENST00000297904.4
PIR-FIGF	NR_037859.2	n.1065+5909A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEGFD	ENST00000297904.4	c.-330A>G		5_prime_UTR_variant	1/7	1	NM_004469.5	P1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 34713 AN: 111633 Hom.: 4493 Cov.: 23 AF XY: 0.305 AC XY: 10331 AN XY: 33847

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.254 AC: 16160 AN: 63742 Hom.: 1626 Cov.: 0 AF XY: 0.316 AC XY: 3688 AN XY: 11658

Gnomad4 AFR exome AF: 0.497

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.383

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.311 AC: 34761 AN: 111686 Hom.: 4496 Cov.: 23 AF XY: 0.306 AC XY: 10375 AN XY: 33910

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.297

Alfa AF: 0.244 Hom.: 16519

Bravo AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.56

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: rs6632528; hg19: chrX-15402398;