4-55089065-T-C

Variant names:

• chr4-55089065-T-C
• rs1531289
• NM_002253.4:c.3405-92A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 32 publications found

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 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000250646 (HGNC:58789):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002253.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	NM_002253.4	MANE Select	c.3405-92A>G		intron	N/A	NP_002244.1	P35968-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	ENST00000263923.5	TSL:1 MANE Select	c.3405-92A>G		intron	N/A	ENSP00000263923.4	P35968-1
	KDR	ENST00000922964.1		c.3063-92A>G		intron	N/A	ENSP00000593023.1
	ENSG00000250646	ENST00000511222.1	TSL:5	n.234-3248T>C		intron	N/A

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

African (AFR) AF: 0.641 AC: 12473 AN: 19458

American (AMR) AF: 0.728 AC: 25785 AN: 35426

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 12340 AN: 21154

East Asian (EAS) AF: 0.790 AC: 26475 AN: 33518

South Asian (SAS) AF: 0.584 AC: 38914 AN: 66676

European-Finnish (FIN) AF: 0.773 AC: 38084 AN: 49278

Middle Eastern (MID) AF: 0.528 AC: 2327 AN: 4404

European-Non Finnish (NFE) AF: 0.706 AC: 336827 AN: 476772

Other (OTH) AF: 0.685 AC: 25035 AN: 36556

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

African (AFR) AF: 0.649 AC: 26909 AN: 41454

American (AMR) AF: 0.725 AC: 11073 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2004 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4151 AN: 5174

South Asian (SAS) AF: 0.577 AC: 2781 AN: 4820

European-Finnish (FIN) AF: 0.784 AC: 8299 AN: 10582

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48104 AN: 67976

Other (OTH) AF: 0.693 AC: 1463 AN: 2112

Alfa AF: 0.691 Hom.: 65967

Bravo AF: 0.691

Asia WGS AF: 0.673 AC: 2339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.55
PhyloP100		-0.087
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1531289; hg19: chr4-55955232;