rs10006115

Positions:

• chr4-55080187-G-T

Variant summary

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

The NM_002253.4(KDR):​c.3849-24C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 1,603,004 control chromosomes in the GnomAD database, including 1,911 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 0.055 (284 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1627 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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]

ENSG00000250646 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.085 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4	c.3849-24C>A		intron_variant		ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.3849-24C>A		intron_variant		1	NM_002253.4	ENSP00000263923.4
ENSG00000250646	ENST00000511222.1	n.233+4945G>T		intron_variant		5
KDR	ENST00000647068.1	n.3862-24C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8350 AN: 152150 Hom.: 284 Cov.: 33

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.0605

Gnomad EAS AF: 0.0920

Gnomad SAS AF: 0.0877

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0407

Gnomad OTH AF: 0.0540

GnomAD3 exomes AF: 0.0499 AC: 12514 AN: 250582 Hom.: 416 AF XY: 0.0523 AC XY: 7084 AN XY: 135432

Gnomad AFR exome AF: 0.0825

Gnomad AMR exome AF: 0.0240

Gnomad ASJ exome AF: 0.0618

Gnomad EAS exome AF: 0.0978

Gnomad SAS exome AF: 0.0819

Gnomad FIN exome AF: 0.0358

Gnomad NFE exome AF: 0.0385

Gnomad OTH exome AF: 0.0476

GnomAD4 exome AF: 0.0426 AC: 61849 AN: 1450736 Hom.: 1627 Cov.: 30 AF XY: 0.0443 AC XY: 31974 AN XY: 722398

Gnomad4 AFR exome AF: 0.0886

Gnomad4 AMR exome AF: 0.0258

Gnomad4 ASJ exome AF: 0.0621

Gnomad4 EAS exome AF: 0.0833

Gnomad4 SAS exome AF: 0.0845

Gnomad4 FIN exome AF: 0.0367

Gnomad4 NFE exome AF: 0.0364

Gnomad4 OTH exome AF: 0.0509

GnomAD4 genome AF: 0.0550 AC: 8374 AN: 152268 Hom.: 284 Cov.: 33 AF XY: 0.0556 AC XY: 4137 AN XY: 74458

Gnomad4 AFR AF: 0.0834

Gnomad4 AMR AF: 0.0301

Gnomad4 ASJ AF: 0.0605

Gnomad4 EAS AF: 0.0919

Gnomad4 SAS AF: 0.0879

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.0406

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0443 Hom.: 66

Bravo AF: 0.0541

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.9
DANN	Benign	0.60

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: rs10006115; hg19: chr4-55946354; COSMIC: COSV55768451;