NM_002253.4:c.3069+576A>G

Variant names:

• chr4-55092041-T-C
• rs1458831
• NM_002253.4:c.3069+576A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002253.4(KDR):​c.3069+576A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 152,234 control chromosomes in the GnomAD database, including 571 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 0.079 (571 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	NM_002253.4	MANE Select	c.3069+576A>G		intron	N/A	NP_002244.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	ENST00000263923.5	TSL:1 MANE Select	c.3069+576A>G		intron	N/A	ENSP00000263923.4
	ENSG00000250646	ENST00000511222.1	TSL:5	n.234-272T>C		intron	N/A
	KDR	ENST00000647068.1		n.3082+576A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0788 AC: 11994 AN: 152116 Hom.: 572 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.0224

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0920

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0787 AC: 11987 AN: 152234 Hom.: 571 Cov.: 32 AF XY: 0.0780 AC XY: 5804 AN XY: 74432

African (AFR) AF: 0.0314 AC: 1306 AN: 41550

American (AMR) AF: 0.0760 AC: 1161 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3470

East Asian (EAS) AF: 0.0222 AC: 115 AN: 5178

South Asian (SAS) AF: 0.0867 AC: 417 AN: 4812

European-Finnish (FIN) AF: 0.112 AC: 1186 AN: 10610

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7354 AN: 68024

Other (OTH) AF: 0.0924 AC: 195 AN: 2110

Alfa AF: 0.101 Hom.: 1038

Bravo AF: 0.0740

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		-0.92
Mutation Taster		=97/3	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: rs1458831; hg19: chr4-55958208;