rs12505758

chr4-55100731-T-C

Variant summary

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

The NM_002253.4(KDR):c.2266+1166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,170 control chromosomes in the GnomAD database, including 1,213 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 0.11 (1213 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

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]

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 (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDR	NM_002253.4	c.2266+1166A>G		intron_variant		ENST00000263923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDR	ENST00000263923.5	c.2266+1166A>G		intron_variant		1	NM_002253.4	P1
KDR	ENST00000647068.1	n.2279+1166A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16179 AN: 152054 Hom.: 1217 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.106 AC: 16165 AN: 152170 Hom.: 1213 Cov.: 32 AF XY: 0.108 AC XY: 8064 AN XY: 74390

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.0813

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.122

Alfa AF: 0.123 Hom.: 445

Bravo AF: 0.103

Asia WGS AF: 0.264 AC: 920 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	7.2
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12505758; hg19: chr4-55966898;