rs12498529

Positions:

• chr4-55084031-A-T

Variant summary

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

The NM_002253.4(KDR):​c.3663-1396T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,176 control chromosomes in the GnomAD database, including 7,259 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 0.28 (7259 hom., cov: 33)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

Genes affected

KDR (HGNC:6307): (kinase insert domain receptor) Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDR	NM_002253.4	c.3663-1396T>A		intron_variant		ENST00000263923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDR	ENST00000263923.5	c.3663-1396T>A		intron_variant		1	NM_002253.4	P1
	ENST00000511222.1	n.234-8282A>T		intron_variant, non_coding_transcript_variant		5
KDR	ENST00000647068.1	n.3676-1396T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42120 AN: 152058 Hom.: 7232 Cov.: 33

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.277 AC: 42192 AN: 152176 Hom.: 7259 Cov.: 33 AF XY: 0.274 AC XY: 20392 AN XY: 74396

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.270

Alfa AF: 0.254 Hom.: 749

Bravo AF: 0.285

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.40

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: rs12498529; hg19: chr4-55950198;