rs17085326

chr4-55111209-C-T

Variant summary

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

The NM_002253.4(KDR):c.977-441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 152,178 control chromosomes in the GnomAD database, including 574 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 0.083 (574 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDR	NM_002253.4	c.977-441G>A		intron_variant		ENST00000263923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDR	ENST00000263923.5	c.977-441G>A		intron_variant		1	NM_002253.4	P1
KDR	ENST00000512566.1	n.977-441G>A		intron_variant, non_coding_transcript_variant		1
KDR	ENST00000647068.1	n.990-441G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0834 AC: 12686 AN: 152060 Hom.: 575 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00772

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.0815

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

GnomAD4 genome AF: 0.0834 AC: 12695 AN: 152178 Hom.: 574 Cov.: 32 AF XY: 0.0845 AC XY: 6288 AN XY: 74400

Gnomad4 AFR AF: 0.0919

Gnomad4 AMR AF: 0.0627

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.00773

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0843

Gnomad4 OTH AF: 0.0802

Alfa AF: 0.0830 Hom.: 247

Bravo AF: 0.0800

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.60
Dann	Benign	0.50

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: rs17085326; hg19: chr4-55977376;