chr4-55114289-C-T

Position:

• chr4-55114289-C-T

Variant summary

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

The ENST00000263923.5(KDR):​c.659-24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,609,320 control chromosomes in the GnomAD database, including 33,028 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 0.16 (2237 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30791 hom.)
• Consequence: KDR ENST00000263923.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4	c.659-24G>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.659-24G>A		intron_variant		1	NM_002253.4	ENSP00000263923	P1
KDR	ENST00000512566.1	n.659-24G>A		intron_variant, non_coding_transcript_variant		1
KDR	ENST00000647068.1	n.672-24G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24560 AN: 152078 Hom.: 2231 Cov.: 32

Gnomad AFR AF: 0.0743

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.178 AC: 44618 AN: 250184 Hom.: 4406 AF XY: 0.184 AC XY: 24896 AN XY: 135294

Gnomad AFR exome AF: 0.0749

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.296

Gnomad EAS exome AF: 0.180

Gnomad SAS exome AF: 0.184

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.201 AC: 293200 AN: 1457124 Hom.: 30791 Cov.: 32 AF XY: 0.202 AC XY: 146389 AN XY: 725170

Gnomad4 AFR exome AF: 0.0707

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.161 AC: 24571 AN: 152196 Hom.: 2237 Cov.: 32 AF XY: 0.158 AC XY: 11768 AN XY: 74390

Gnomad4 AFR AF: 0.0743

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.181

Alfa AF: 0.182 Hom.: 1791

Bravo AF: 0.158

Asia WGS AF: 0.213 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2305949; hg19: chr4-55980456; COSMIC: COSV55758738;