chr4-55094992-T-C

Position:

• chr4-55094992-T-C

Variant summary

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

The NM_002253.4(KDR):​c.2818-37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,600,124 control chromosomes in the GnomAD database, including 46,516 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 0.22 (3938 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42578 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512

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]

KDR (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 (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4	c.2818-37A>G		intron_variant		ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.2818-37A>G		intron_variant		1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000509309.1	n.582-37A>G		intron_variant		3
KDR	ENST00000647068.1	n.2831-37A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32907 AN: 152016 Hom.: 3931 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.225 AC: 56006 AN: 249140 Hom.: 7404 AF XY: 0.226 AC XY: 30484 AN XY: 134734

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.100

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.473

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.236 AC: 341504 AN: 1447990 Hom.: 42578 Cov.: 27 AF XY: 0.234 AC XY: 169126 AN XY: 721336

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.436

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.217 AC: 32941 AN: 152134 Hom.: 3938 Cov.: 32 AF XY: 0.219 AC XY: 16289 AN XY: 74368

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.216

Alfa AF: 0.230 Hom.: 6468

Bravo AF: 0.201

Asia WGS AF: 0.305 AC: 1059 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	0.62
DANN	Benign	0.23

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: rs2219471; hg19: chr4-55961159; COSMIC: COSV55764437; COSMIC: COSV55764437;