dbSNP rs56233104: KDR:c.-1G>T (chr4-55125294-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

10 publications found

Variant links:

COSMIC-nc: COSV55759034

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

KDR links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002253.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 135552.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0558 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	NM_002253.4	MANE Select	c.-1G>T		5_prime_UTR	Exon 1 of 30	NP_002244.1	P35968-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KDR	ENST00000263923.5	TSL:1 MANE Select	c.-1G>T	5_prime_UTR	Exon 1 of 30	ENSP00000263923.4	P35968-1
KDR	ENST00000922964.1		c.-1G>T	5_prime_UTR	Exon 1 of 29	ENSP00000593023.1
KDR	ENST00000512566.1	TSL:1	n.-1G>T	upstream_gene	N/A

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

GnomAD2 exomes

AF:

0.0368

AC:

8907

AN:

241940

AF XY:

0.0370

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 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

African (AFR)

AF:

0.0163

AC:

544

AN:

33456

American (AMR)

AF:

0.0253

AC:

1123

AN:

44458

Ashkenazi Jewish (ASJ)

AF:

0.0469

AC:

1220

AN:

26024

East Asian (EAS)

AF:

0.000126

AC:

AN:

39636

South Asian (SAS)

AF:

0.0119

AC:

1014

AN:

85554

European-Finnish (FIN)

AF:

0.0222

AC:

1171

AN:

52756

Middle Eastern (MID)

AF:

0.0544

AC:

313

AN:

5754

European-Non Finnish (NFE)

AF:

0.0602

AC:

66829

AN:

1111026

Other (OTH)

AF:

0.0420

AC:

2532

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

4058

8116

12174

16232

20290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2434

4868

7302

9736

12170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0370

AC:

5643

AN:

152336

Hom.:

142

Cov.:

AF XY:

0.0340

AC XY:

2530

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0167

AC:

696

AN:

41578

American (AMR)

AF:

0.0328

AC:

502

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0447

AC:

155

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5168

South Asian (SAS)

AF:

0.0135

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0186

AC:

198

AN:

10630

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0573

AC:

3900

AN:

68028

Other (OTH)

AF:

0.0388

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

283

566

850

1133

1416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0503

Hom.:

Bravo

AF:

0.0372

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

KDR-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

1.9

PromoterAI

0.035

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over