chr4-55125564-T-C

Variant names:

• chr4-55125564-T-C
• rs7667298
• NM_002253.4:c.-271A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002253.4(KDR):​c.-271A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 590,418 control chromosomes in the GnomAD database, including 85,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.49 (19238 hom., cov: 33)
  • Exomes 𝑓: 0.55 (66472 hom.)
• Consequence: KDR NM_002253.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 55 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 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.-271A>G		5_prime_UTR	Exon 1 of 30	NP_002244.1	P35968-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	ENST00000263923.5	TSL:1 MANE Select	c.-271A>G		5_prime_UTR	Exon 1 of 30	ENSP00000263923.4	P35968-1
	KDR	ENST00000922964.1		c.-271A>G		5_prime_UTR	Exon 1 of 29	ENSP00000593023.1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74391 AN: 151868 Hom.: 19214 Cov.: 33

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.546 AC: 239214 AN: 438430 Hom.: 66472 Cov.: 3 AF XY: 0.543 AC XY: 125403 AN XY: 231154

African (AFR) AF: 0.324 AC: 3928 AN: 12134

American (AMR) AF: 0.650 AC: 12060 AN: 18546

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 6811 AN: 13324

East Asian (EAS) AF: 0.729 AC: 22436 AN: 30774

South Asian (SAS) AF: 0.471 AC: 21425 AN: 45516

European-Finnish (FIN) AF: 0.583 AC: 16747 AN: 28748

Middle Eastern (MID) AF: 0.484 AC: 914 AN: 1888

European-Non Finnish (NFE) AF: 0.540 AC: 141561 AN: 262256

Other (OTH) AF: 0.528 AC: 13332 AN: 25244

GnomAD4 genome AF: 0.490 AC: 74461 AN: 151988 Hom.: 19238 Cov.: 33 AF XY: 0.494 AC XY: 36694 AN XY: 74272

African (AFR) AF: 0.323 AC: 13405 AN: 41498

American (AMR) AF: 0.598 AC: 9145 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1720 AN: 3468

East Asian (EAS) AF: 0.665 AC: 3384 AN: 5092

South Asian (SAS) AF: 0.467 AC: 2251 AN: 4816

European-Finnish (FIN) AF: 0.598 AC: 6332 AN: 10594

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36629 AN: 67904

Other (OTH) AF: 0.515 AC: 1086 AN: 2110

Alfa AF: 0.521 Hom.: 32303

Bravo AF: 0.486

Asia WGS AF: 0.553 AC: 1924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.6
DANN	Benign	0.43
PhyloP100		-1.0
PromoterAI		0.21	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7667298; hg19: chr4-55991731;