4-55120395-G-A

Variant names:

• chr4-55120395-G-A
• rs1531290
• NM_002253.4:c.161+702C>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.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
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.741 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	NM_002253.4	MANE Select	c.161+702C>T		intron	N/A	NP_002244.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	ENST00000263923.5	TSL:1 MANE Select	c.161+702C>T		intron	N/A	ENSP00000263923.4
	KDR	ENST00000512566.1	TSL:1	n.161+702C>T		intron	N/A
	KDR	ENST00000647068.1		n.174+702C>T		intron	N/A

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

African (AFR) AF: 0.748 AC: 30970 AN: 41416

American (AMR) AF: 0.646 AC: 9857 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3470

East Asian (EAS) AF: 0.743 AC: 3829 AN: 5150

South Asian (SAS) AF: 0.706 AC: 3390 AN: 4802

European-Finnish (FIN) AF: 0.618 AC: 6516 AN: 10540

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35216 AN: 67928

Other (OTH) AF: 0.579 AC: 1221 AN: 2110

Alfa AF: 0.553 Hom.: 46689

Bravo AF: 0.622

Asia WGS AF: 0.698 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.054
DANN	Benign	0.54
PhyloP100		-2.9
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: rs1531290; hg19: chr4-55986562;