4-55089065-T-C

Position:

• chr4-55089065-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.3405-92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 895,314 control chromosomes in the GnomAD database, including 219,353 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 0.69 (36913 hom., cov: 32)
  • Exomes 𝑓: 0.70 (182440 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4	c.3405-92A>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.3405-92A>G		intron_variant		1	NM_002253.4	ENSP00000263923.4
ENSG00000250646	ENST00000511222.1	n.234-3248T>C		intron_variant		5
KDR	ENST00000647068.1	n.3418-92A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105546 AN: 151954 Hom.: 36867 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.689

GnomAD4 exome AF: 0.697 AC: 518260 AN: 743242 Hom.: 182440 AF XY: 0.693 AC XY: 270988 AN XY: 391310

Gnomad4 AFR exome AF: 0.641

Gnomad4 AMR exome AF: 0.728

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.773

Gnomad4 NFE exome AF: 0.706

Gnomad4 OTH exome AF: 0.685

GnomAD4 genome AF: 0.695 AC: 105653 AN: 152072 Hom.: 36913 Cov.: 32 AF XY: 0.697 AC XY: 51796 AN XY: 74342

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.784

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.693

Alfa AF: 0.689 Hom.: 46866

Bravo AF: 0.691

Asia WGS AF: 0.673 AC: 2339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.55

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: rs1531289; hg19: chr4-55955232;