4-55100634-C-T

Variant names:

• chr4-55100634-C-T
• rs6828477
• NM_002253.4:c.2266+1263G>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.2266+1263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,058 control chromosomes in the GnomAD database, including 27,064 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 0.59 (27064 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• Publications: 23 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.2266+1263G>A		intron_variant	Intron 15 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.2266+1263G>A		intron_variant	Intron 15 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000647068.1	n.2279+1263G>A		intron_variant	Intron 15 of 29

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90035 AN: 151940 Hom.: 27029 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.593 AC: 90130 AN: 152058 Hom.: 27064 Cov.: 32 AF XY: 0.598 AC XY: 44431 AN XY: 74344

African (AFR) AF: 0.541 AC: 22433 AN: 41456

American (AMR) AF: 0.640 AC: 9769 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1805 AN: 3472

East Asian (EAS) AF: 0.775 AC: 4017 AN: 5180

South Asian (SAS) AF: 0.483 AC: 2328 AN: 4820

European-Finnish (FIN) AF: 0.674 AC: 7128 AN: 10572

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40595 AN: 67978

Other (OTH) AF: 0.579 AC: 1222 AN: 2110

Alfa AF: 0.590 Hom.: 79288

Bravo AF: 0.590

Asia WGS AF: 0.609 AC: 2118 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	0.75
DANN	Benign	0.54
PhyloP100		-0.98
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: rs6828477; hg19: chr4-55966801;