rs11133360

Variant names:

• chr4-55116585-C-T
• rs11133360
• NM_002253.4:c.359-1174G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002253.4(KDR):​c.359-1174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,878 control chromosomes in the GnomAD database, including 19,893 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 0.51 (19893 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 33 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.359-1174G>A		intron_variant	Intron 3 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.359-1174G>A		intron_variant	Intron 3 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000512566.1	n.359-1174G>A		intron_variant	Intron 3 of 12	1
KDR	ENST00000647068.1	n.372-1174G>A		intron_variant	Intron 3 of 29

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77040 AN: 151758 Hom.: 19890 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.507 AC: 77070 AN: 151878 Hom.: 19893 Cov.: 32 AF XY: 0.507 AC XY: 37626 AN XY: 74218

African (AFR) AF: 0.423 AC: 17486 AN: 41376

American (AMR) AF: 0.443 AC: 6756 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2338 AN: 3472

East Asian (EAS) AF: 0.634 AC: 3265 AN: 5152

South Asian (SAS) AF: 0.682 AC: 3278 AN: 4808

European-Finnish (FIN) AF: 0.544 AC: 5746 AN: 10554

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36322 AN: 67948

Other (OTH) AF: 0.530 AC: 1119 AN: 2112

Alfa AF: 0.530 Hom.: 16787

Bravo AF: 0.495

Asia WGS AF: 0.666 AC: 2316 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	4.1
DANN	Benign	0.38
PhyloP100		0.33
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: rs11133360; hg19: chr4-55982752;