4-55100286-C-T

Position:

• chr4-55100286-C-T

Variant summary

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

The ENST00000263923.5(KDR):​c.2267-1483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,100 control chromosomes in the GnomAD database, including 3,823 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 0.21 (3823 hom., cov: 32)
• Consequence: KDR ENST00000263923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4	c.2267-1483G>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.2267-1483G>A		intron_variant		1	NM_002253.4	ENSP00000263923	P1
KDR	ENST00000647068.1	n.2280-1483G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32052 AN: 151982 Hom.: 3818 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.211 AC: 32069 AN: 152100 Hom.: 3823 Cov.: 32 AF XY: 0.214 AC XY: 15904 AN XY: 74340

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.210

Alfa AF: 0.226 Hom.: 678

Bravo AF: 0.196

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.59

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: rs1870378; hg19: chr4-55966453;