rs12642307

Positions:

• chr4-55086014-T-C
• chr4-55086014-T-G

Variant summary

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

The NM_002253.4(KDR):​c.3662+1593A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,100 control chromosomes in the GnomAD database, including 5,187 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 0.26 (5187 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4	c.3662+1593A>G		intron_variant		ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.3662+1593A>G		intron_variant		1	NM_002253.4	ENSP00000263923	P1
	ENST00000511222.1	n.234-6299T>C		intron_variant, non_coding_transcript_variant		5
KDR	ENST00000647068.1	n.3675+1593A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38882 AN: 151982 Hom.: 5188 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0801

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.256 AC: 38885 AN: 152100 Hom.: 5187 Cov.: 32 AF XY: 0.258 AC XY: 19151 AN XY: 74360

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.0795

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.234

Alfa AF: 0.264 Hom.: 2519

Bravo AF: 0.247

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.26

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: rs12642307; hg19: chr4-55952181;