Variant rs56233104 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_002253.4(KDR):c.-1G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 1,611,238 control chromosomes in the GnomAD database, including 2,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.037 ( 142 hom., cov: 33)

Exomes 𝑓: 0.051 ( 2142 hom. )

Consequence

KDR
NM_002253.4 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1O:1

Conservation

PhyloP100: 1.94

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 4-55125294-C-A is Benign according to our data. Variant chr4-55125294-C-A is described in ClinVar as [Benign]. Clinvar id is 135552.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-55125294-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4 linkuse as main transcript	c.-1G>T		5_prime_UTR_variant	1/30	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5 linkuse as main transcript	c.-1G>T		5_prime_UTR_variant	1/30	1	NM_002253.4	ENSP00000263923	P1	P35968-1
KDR	ENST00000512566.1 linkuse as main transcript			upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

5641

AN:

152218

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.0447

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0573

Gnomad OTH

AF:

0.0392

GnomAD3 exomes

AF:

0.0368

AC:

8907

AN:

241940

Hom.:

199

AF XY:

0.0370

AC XY:

4873

AN XY:

131526

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.0234

Gnomad ASJ exome

AF:

0.0462

Gnomad EAS exome

AF:

0.000332

Gnomad SAS exome

AF:

0.0115

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.0589

Gnomad OTH exome

AF:

0.0448

GnomAD4 exome

AF:

0.0512

AC:

74751

AN:

1458902

Hom.:

2142

Cov.:

AF XY:

0.0502

AC XY:

36439

AN XY:

725528

show subpopulations

Gnomad4 AFR exome

AF:

0.0163

Gnomad4 AMR exome

AF:

0.0253

Gnomad4 ASJ exome

AF:

0.0469

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.0222

Gnomad4 NFE exome

AF:

0.0602

Gnomad4 OTH exome

AF:

0.0420

GnomAD4 genome

AF:

0.0370

AC:

5643

AN:

152336

Hom.:

142

Cov.:

AF XY:

0.0340

AC XY:

2530

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0167

Gnomad4 AMR

AF:

0.0328

Gnomad4 ASJ

AF:

0.0447

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.0186

Gnomad4 NFE

AF:

0.0573

Gnomad4 OTH

AF:

0.0388

Alfa

AF:

0.0503

Hom.:

Bravo

AF:

0.0372

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KDR-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 23, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over