chr4-55100286-C-T

Variant names:

• chr4-55100286-C-T
• rs1870378
• NM_002253.4:c.2267-1483G>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.2267-1483G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,100 control chromosomes in the GnomAD database, including 3,823 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 0.21 (3823 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.2267-1483G>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.2267-1483G>A		intron_variant	Intron 15 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000647068.1	n.2280-1483G>A		intron_variant	Intron 15 of 29

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32052 AN: 151982 Hom.: 3818 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.211 AC: 32069 AN: 152100 Hom.: 3823 Cov.: 32 AF XY: 0.214 AC XY: 15904 AN XY: 74340

African (AFR) AF: 0.119 AC: 4952 AN: 41512

American (AMR) AF: 0.154 AC: 2348 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 713 AN: 3472

East Asian (EAS) AF: 0.466 AC: 2408 AN: 5172

South Asian (SAS) AF: 0.180 AC: 868 AN: 4818

European-Finnish (FIN) AF: 0.306 AC: 3238 AN: 10568

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16689 AN: 67970

Other (OTH) AF: 0.210 AC: 444 AN: 2112

Alfa AF: 0.226 Hom.: 678

Bravo AF: 0.196

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.59
PhyloP100		-0.45
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: rs1870378; hg19: chr4-55966453;