Variant 4-55081941-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002253.4(KDR):c.3848+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,579,230 control chromosomes in the GnomAD database, including 787,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 1.0 ( 75710 hom., cov: 32)

Exomes 𝑓: 1.0 ( 712184 hom. )

Consequence

KDR
NM_002253.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.0530

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-55081941-A-G is Benign according to our data. Variant chr4-55081941-A-G is described in ClinVar as [Benign]. Clinvar id is 518355.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-55081941-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4 link	c.3848+15T>C		intron_variant		ENST00000263923.5	NP_002244.1	P35968-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
KDR	ENST00000263923.5 link	c.3848+15T>C	intron_variant	1	NM_002253.4	ENSP00000263923.4	P35968-1
ENSG00000250646	ENST00000511222.1 link	n.233+6699A>G	intron_variant	5
KDR	ENST00000647068.1 link	n.3861+15T>C	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.997

AC:

151765

AN:

152228

Hom.:

75651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.992

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.997

Gnomad ASJ

AF:

0.995

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.997

GnomAD3 exomes

AF:

0.999

AC:

250551

AN:

250914

Hom.:

125094

AF XY:

0.999

AC XY:

135431

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.992

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

0.995

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.996

GnomAD4 exome

AF:

0.999

AC:

1425623

AN:

1426884

Hom.:

712184

Cov.:

AF XY:

0.999

AC XY:

711743

AN XY:

712348

show subpopulations

Gnomad4 AFR exome

AF:

0.992

Gnomad4 AMR exome

AF:

0.997

Gnomad4 ASJ exome

AF:

0.996

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.998

GnomAD4 genome

AF:

0.997

AC:

151883

AN:

152346

Hom.:

75710

Cov.:

AF XY:

0.997

AC XY:

74276

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.992

Gnomad4 AMR

AF:

0.997

Gnomad4 ASJ

AF:

0.995

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.997

Alfa

AF:

0.998

Hom.:

13910

Bravo

AF:

0.996

Asia WGS

AF:

1.00

AC:

3473

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Capillary infantile hemangioma

Benign:1

Benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.2

DANN

Benign

0.63

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over