chr4-55086014-T-C

Variant names:

• chr4-55086014-T-C
• rs12642307
• NM_002253.4:c.3662+1593A>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.3662+1593A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,100 control chromosomes in the GnomAD database, including 5,187 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 0.26 (5187 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 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.3662+1593A>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.3662+1593A>G		intron	N/A	ENSP00000263923.4
	ENSG00000250646	ENST00000511222.1	TSL:5	n.234-6299T>C		intron	N/A
	KDR	ENST00000647068.1		n.3675+1593A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38882 AN: 151982 Hom.: 5188 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0801

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.256 AC: 38885 AN: 152100 Hom.: 5187 Cov.: 32 AF XY: 0.258 AC XY: 19151 AN XY: 74360

African (AFR) AF: 0.216 AC: 8970 AN: 41480

American (AMR) AF: 0.251 AC: 3842 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3468

East Asian (EAS) AF: 0.0795 AC: 412 AN: 5180

South Asian (SAS) AF: 0.223 AC: 1073 AN: 4822

European-Finnish (FIN) AF: 0.323 AC: 3421 AN: 10580

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19294 AN: 67980

Other (OTH) AF: 0.234 AC: 493 AN: 2106

Alfa AF: 0.269 Hom.: 11270

Bravo AF: 0.247

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.26
PhyloP100		-0.40
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: rs12642307; hg19: chr4-55952181;