rs7654599

Variant names:

• chr4-55110001-C-T
• rs7654599
• NM_002253.4:c.1255+402G>A

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+402G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,026 control chromosomes in the GnomAD database, including 24,941 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 0.57 (24941 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 11 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 (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.1255+402G>A		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+402G>A		intron_variant	Intron 9 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000512566.1	n.1255+402G>A		intron_variant	Intron 9 of 12	1
KDR	ENST00000647068.1	n.1268+402G>A		intron_variant	Intron 9 of 29

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86032 AN: 151908 Hom.: 24910 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.567 AC: 86127 AN: 152026 Hom.: 24941 Cov.: 32 AF XY: 0.571 AC XY: 42440 AN XY: 74300

African (AFR) AF: 0.461 AC: 19086 AN: 41442

American (AMR) AF: 0.625 AC: 9549 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1802 AN: 3470

East Asian (EAS) AF: 0.773 AC: 3983 AN: 5152

South Asian (SAS) AF: 0.469 AC: 2259 AN: 4812

European-Finnish (FIN) AF: 0.674 AC: 7138 AN: 10584

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40415 AN: 67966

Other (OTH) AF: 0.554 AC: 1169 AN: 2112

Alfa AF: 0.580 Hom.: 22535

Bravo AF: 0.561

Asia WGS AF: 0.593 AC: 2062 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	0.34
DANN	Benign	0.40
PhyloP100		-0.79
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: rs7654599; hg19: chr4-55976168;