4-55110284-G-A

Variant names:

• chr4-55110284-G-A
• rs3828550
• NM_002253.4:c.1255+119C>T

Variant summary

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

The NM_002253.4(KDR):​c.1255+119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,074,440 control chromosomes in the GnomAD database, including 62,868 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 0.33 (8298 hom., cov: 32)
  • Exomes 𝑓: 0.34 (54570 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 10 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.1255+119C>T		intron_variant	Intron 9 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.1255+119C>T		intron_variant	Intron 9 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000512566.1	n.1255+119C>T		intron_variant	Intron 9 of 12	1
KDR	ENST00000647068.1	n.1268+119C>T		intron_variant	Intron 9 of 29

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49729 AN: 151870 Hom.: 8281 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.341 AC: 314603 AN: 922452 Hom.: 54570 AF XY: 0.337 AC XY: 161661 AN XY: 479414

African (AFR) AF: 0.267 AC: 5946 AN: 22234

American (AMR) AF: 0.545 AC: 22452 AN: 41178

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 6872 AN: 22426

East Asian (EAS) AF: 0.309 AC: 10836 AN: 35066

South Asian (SAS) AF: 0.287 AC: 20712 AN: 72058

European-Finnish (FIN) AF: 0.357 AC: 18079 AN: 50692

Middle Eastern (MID) AF: 0.260 AC: 1218 AN: 4680

European-Non Finnish (NFE) AF: 0.340 AC: 214515 AN: 631604

Other (OTH) AF: 0.329 AC: 13973 AN: 42514

GnomAD4 genome AF: 0.328 AC: 49777 AN: 151988 Hom.: 8298 Cov.: 32 AF XY: 0.329 AC XY: 24464 AN XY: 74300

African (AFR) AF: 0.268 AC: 11110 AN: 41434

American (AMR) AF: 0.462 AC: 7052 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1517 AN: 5168

South Asian (SAS) AF: 0.280 AC: 1347 AN: 4814

European-Finnish (FIN) AF: 0.348 AC: 3668 AN: 10548

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22912 AN: 67970

Other (OTH) AF: 0.331 AC: 697 AN: 2108

Alfa AF: 0.342 Hom.: 2126

Bravo AF: 0.338

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3828550; hg19: chr4-55976451; COSMIC: COSV55763712;