chr4-55090669-G-A

Variant names:

• chr4-55090669-G-A
• rs7671745
• NM_002253.4:c.3070-591C>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.3070-591C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,818 control chromosomes in the GnomAD database, including 7,680 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 0.32 (7680 hom., cov: 31)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 9 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

ENSG00000250646 (HGNC:58789):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 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.3070-591C>T		intron	N/A	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.3070-591C>T		intron	N/A	ENSP00000263923.4	P35968-1
	KDR	ENST00000922964.1		c.2728-591C>T		intron	N/A	ENSP00000593023.1
	ENSG00000250646	ENST00000511222.1	TSL:5	n.234-1644G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47833 AN: 151700 Hom.: 7666 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.315 AC: 47885 AN: 151818 Hom.: 7680 Cov.: 31 AF XY: 0.317 AC XY: 23525 AN XY: 74208

African (AFR) AF: 0.263 AC: 10891 AN: 41396

American (AMR) AF: 0.234 AC: 3566 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 900 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1706 AN: 5152

South Asian (SAS) AF: 0.263 AC: 1261 AN: 4800

European-Finnish (FIN) AF: 0.428 AC: 4505 AN: 10526

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23919 AN: 67918

Other (OTH) AF: 0.326 AC: 688 AN: 2112

Alfa AF: 0.333 Hom.: 14465

Bravo AF: 0.297

Asia WGS AF: 0.329 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.18
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: rs7671745; hg19: chr4-55956836;