Variant 4-55080187-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002253.4(KDR):c.3849-24C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 1,603,004 control chromosomes in the GnomAD database, including 1,911 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 0.055 ( 284 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1627 hom. )

Consequence

KDR
NM_002253.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.47

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:

ENSG00000250646 (HGNC:):

ENSG00000250646 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.085 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.3849-24C>A		intron_variant		ENST00000263923.5	NP_002244.1	P35968-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
KDR	ENST00000263923.5 linkuse as main transcript	c.3849-24C>A	intron_variant	1	NM_002253.4	ENSP00000263923.4	P35968-1
ENSG00000250646	ENST00000511222.1 linkuse as main transcript	n.233+4945G>T	intron_variant	5
KDR	ENST00000647068.1 linkuse as main transcript	n.3862-24C>A	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8350

AN:

152150

Hom.:

284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0829

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0302

Gnomad ASJ

AF:

0.0605

Gnomad EAS

AF:

0.0920

Gnomad SAS

AF:

0.0877

Gnomad FIN

AF:

0.0399

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0407

Gnomad OTH

AF:

0.0540

GnomAD3 exomes

AF:

0.0499

AC:

12514

AN:

250582

Hom.:

416

AF XY:

0.0523

AC XY:

7084

AN XY:

135432

show subpopulations

Gnomad AFR exome

AF:

0.0825

Gnomad AMR exome

AF:

0.0240

Gnomad ASJ exome

AF:

0.0618

Gnomad EAS exome

AF:

0.0978

Gnomad SAS exome

AF:

0.0819

Gnomad FIN exome

AF:

0.0358

Gnomad NFE exome

AF:

0.0385

Gnomad OTH exome

AF:

0.0476

GnomAD4 exome

AF:

0.0426

AC:

61849

AN:

1450736

Hom.:

1627

Cov.:

AF XY:

0.0443

AC XY:

31974

AN XY:

722398

show subpopulations

Gnomad4 AFR exome

AF:

0.0886

Gnomad4 AMR exome

AF:

0.0258

Gnomad4 ASJ exome

AF:

0.0621

Gnomad4 EAS exome

AF:

0.0833

Gnomad4 SAS exome

AF:

0.0845

Gnomad4 FIN exome

AF:

0.0367

Gnomad4 NFE exome

AF:

0.0364

Gnomad4 OTH exome

AF:

0.0509

GnomAD4 genome

AF:

0.0550

AC:

8374

AN:

152268

Hom.:

284

Cov.:

AF XY:

0.0556

AC XY:

4137

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0834

Gnomad4 AMR

AF:

0.0301

Gnomad4 ASJ

AF:

0.0605

Gnomad4 EAS

AF:

0.0919

Gnomad4 SAS

AF:

0.0879

Gnomad4 FIN

AF:

0.0399

Gnomad4 NFE

AF:

0.0406

Gnomad4 OTH

AF:

0.0539

Alfa

AF:

0.0443

Hom.:

Bravo

AF:

0.0541

Asia WGS

AF:

0.0900

AC:

312

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.9

DANN

Benign

0.60

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over