rs7671745

chr4-55090669-G-Achr4-55090669-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDR	NM_002253.4	c.3070-591C>T		intron_variant		ENST00000263923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDR	ENST00000263923.5	c.3070-591C>T		intron_variant		1	NM_002253.4	P1
	ENST00000511222.1	n.234-1644G>A		intron_variant, non_coding_transcript_variant		5
KDR	ENST00000647068.1	n.3083-591C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.326

Alfa AF: 0.333 Hom.: 1620

Bravo AF: 0.297

Asia WGS AF: 0.329 AC: 1143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.18

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: rs7671745; hg19: chr4-55956836;