X-15348057-G-T

Variant names:

• chrX-15348057-G-T
• rs6527518
• NM_004469.5:c.743-698C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004469.5(VEGFD):​c.743-698C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 110,662 control chromosomes in the GnomAD database, including 7,572 homozygotes. There are 14,586 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 0.44 (7572 hom., 14586 hem., cov: 23)
• Consequence: VEGFD NM_004469.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VEGFD	NM_004469.5	c.743-698C>A		intron_variant	Intron 5 of 6	ENST00000297904.4	NP_004460.1
PIR-FIGF	NR_037859.2	n.1718-698C>A		intron_variant	Intron 13 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VEGFD	ENST00000297904.4	c.743-698C>A		intron_variant	Intron 5 of 6	1	NM_004469.5	ENSP00000297904.3

Frequencies

GnomAD3 genomes AF: 0.440 AC: 48685 AN: 110612 Hom.: 7578 Cov.: 23

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.440 AC: 48697 AN: 110662 Hom.: 7572 Cov.: 23 AF XY: 0.443 AC XY: 14586 AN XY: 32930

African (AFR) AF: 0.433 AC: 13087 AN: 30202

American (AMR) AF: 0.385 AC: 4060 AN: 10546

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1019 AN: 2632

East Asian (EAS) AF: 0.415 AC: 1453 AN: 3499

South Asian (SAS) AF: 0.581 AC: 1528 AN: 2631

European-Finnish (FIN) AF: 0.472 AC: 2772 AN: 5871

Middle Eastern (MID) AF: 0.424 AC: 92 AN: 217

European-Non Finnish (NFE) AF: 0.450 AC: 23788 AN: 52871

Other (OTH) AF: 0.438 AC: 663 AN: 1514

Alfa AF: 0.373 Hom.: 3306

Bravo AF: 0.429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		1.6
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: rs6527518; hg19: chrX-15366179;