rs13135562

chr4-55102578-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002253.4(KDR):c.1988-70G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,545,956 control chromosomes in the GnomAD database, including 225 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 0.012 (19 hom., cov: 33)
  • Exomes 𝑓: 0.016 (206 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0115 (1753/152278) while in subpopulation NFE AF= 0.0198 (1348/68020). AF 95% confidence interval is 0.0189. There are 19 homozygotes in gnomad4. There are 845 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1753 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDR	NM_002253.4	c.1988-70G>C		intron_variant		ENST00000263923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDR	ENST00000263923.5	c.1988-70G>C		intron_variant		1	NM_002253.4	P1
KDR	ENST00000647068.1	n.2001-70G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1753 AN: 152160 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.00335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.00943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.00670

GnomAD4 exome AF: 0.0162 AC: 22519 AN: 1393678 Hom.: 206 AF XY: 0.0158 AC XY: 11006 AN XY: 696520

Gnomad4 AFR exome AF: 0.00271

Gnomad4 AMR exome AF: 0.00400

Gnomad4 ASJ exome AF: 0.00990

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00599

Gnomad4 FIN exome AF: 0.0119

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.0115 AC: 1753 AN: 152278 Hom.: 19 Cov.: 33 AF XY: 0.0113 AC XY: 845 AN XY: 74454

Gnomad4 AFR AF: 0.00334

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00943

Gnomad4 NFE AF: 0.0198

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.0191 Hom.: 4

Bravo AF: 0.0104

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.6
Dann	Benign	0.43

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: rs13135562; hg19: chr4-55968745;