rs17711073

Variant names:

• chr4-55111993-T-C
• rs17711073
• NM_002253.4:c.977-1225A>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.977-1225A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 152,284 control chromosomes in the GnomAD database, including 378 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 0.068 (378 hom., cov: 33)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 4 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 (NFE) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.977-1225A>G		intron_variant	Intron 7 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.977-1225A>G		intron_variant	Intron 7 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000512566.1	n.977-1225A>G		intron_variant	Intron 7 of 12	1
KDR	ENST00000647068.1	n.990-1225A>G		intron_variant	Intron 7 of 29

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10328 AN: 152166 Hom.: 376 Cov.: 33

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.0721

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0679 AC: 10341 AN: 152284 Hom.: 378 Cov.: 33 AF XY: 0.0687 AC XY: 5116 AN XY: 74466

African (AFR) AF: 0.0609 AC: 2531 AN: 41566

American (AMR) AF: 0.0555 AC: 849 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 325 AN: 3472

East Asian (EAS) AF: 0.0133 AC: 69 AN: 5184

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4832

European-Finnish (FIN) AF: 0.103 AC: 1089 AN: 10620

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0750 AC: 5101 AN: 67992

Other (OTH) AF: 0.0709 AC: 150 AN: 2116

Alfa AF: 0.0658 Hom.: 313

Bravo AF: 0.0643

Asia WGS AF: 0.0300 AC: 104 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.99
DANN	Benign	0.44
PhyloP100		-0.30
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: rs17711073; hg19: chr4-55978160;