rs7667298

Positions:

• chr4-55125564-T-C
• chr4-55125564-T-G

Variant summary

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

The NM_002253.4(KDR):​c.-271A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 590,418 control chromosomes in the GnomAD database, including 85,710 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 0.49 (19238 hom., cov: 33)
  • Exomes 𝑓: 0.55 (66472 hom.)
• Consequence: KDR NM_002253.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4	c.-271A>G		5_prime_UTR_variant	1/30	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.-271A>G		5_prime_UTR_variant	1/30	1	NM_002253.4	ENSP00000263923.4

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74391 AN: 151868 Hom.: 19214 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.546 AC: 239214 AN: 438430 Hom.: 66472 Cov.: 3 AF XY: 0.543 AC XY: 125403 AN XY: 231154

Gnomad4 AFR exome AF: 0.324

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.511

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.528

GnomAD4 genome AF: 0.490 AC: 74461 AN: 151988 Hom.: 19238 Cov.: 33 AF XY: 0.494 AC XY: 36694 AN XY: 74272

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.515

Alfa AF: 0.445 Hom.: 2952

Bravo AF: 0.486

Asia WGS AF: 0.553 AC: 1924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.6
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7667298; hg19: chr4-55991731;