rs1531290

Positions:

• chr4-55120395-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002253.4(KDR):​c.161+702C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,890 control chromosomes in the GnomAD database, including 29,686 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 0.62 (29686 hom., cov: 30)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4	c.161+702C>T		intron_variant		ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.161+702C>T		intron_variant		1	NM_002253.4	ENSP00000263923	P1
KDR	ENST00000512566.1	n.161+702C>T		intron_variant, non_coding_transcript_variant		1
KDR	ENST00000647068.1	n.174+702C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93523 AN: 151774 Hom.: 29638 Cov.: 30

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.616 AC: 93624 AN: 151890 Hom.: 29686 Cov.: 30 AF XY: 0.626 AC XY: 46452 AN XY: 74230

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.579

Alfa AF: 0.554 Hom.: 13373

Bravo AF: 0.622

Asia WGS AF: 0.698 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.054
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs1531290; hg19: chr4-55986562;