rs10008360

Variant names:

• chr4-55086239-G-A
• rs10008360
• NM_002253.4:c.3662+1368C>T

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+1368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,130 control chromosomes in the GnomAD database, including 3,130 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 0.12 (3130 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586
• Publications: 2 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 (AFR) allele frequency at 95% confidence interval = 0.376 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+1368C>T		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+1368C>T		intron	N/A	ENSP00000263923.4
	ENSG00000250646	ENST00000511222.1	TSL:5	n.234-6074G>A		intron	N/A
	KDR	ENST00000647068.1		n.3675+1368C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18731 AN: 152012 Hom.: 3110 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0649

Gnomad ASJ AF: 0.0260

Gnomad EAS AF: 0.00905

Gnomad SAS AF: 0.0339

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0912

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

GnomAD4 genome AF: 0.124 AC: 18799 AN: 152130 Hom.: 3130 Cov.: 32 AF XY: 0.121 AC XY: 9004 AN XY: 74394

African (AFR) AF: 0.381 AC: 15784 AN: 41432

American (AMR) AF: 0.0647 AC: 989 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0260 AC: 90 AN: 3464

East Asian (EAS) AF: 0.00907 AC: 47 AN: 5182

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4828

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10616

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0216 AC: 1471 AN: 68012

Other (OTH) AF: 0.0902 AC: 190 AN: 2106

Alfa AF: 0.0631 Hom.: 1907

Bravo AF: 0.138

Asia WGS AF: 0.0460 AC: 162 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	0.87
DANN	Benign	0.19
PhyloP100		-0.59
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: rs10008360; hg19: chr4-55952406;