4-55104513-G-A

Position:

• chr4-55104513-G-A

Variant summary

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

The NM_002253.4(KDR):​c.1987+130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 742,436 control chromosomes in the GnomAD database, including 44,324 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 0.30 (7746 hom., cov: 32)
  • Exomes 𝑓: 0.35 (36578 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDR	NM_002253.4	c.1987+130C>T		intron_variant		ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.1987+130C>T		intron_variant		1	NM_002253.4	ENSP00000263923	P1
KDR	ENST00000647068.1	n.2000+130C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46077 AN: 151780 Hom.: 7729 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.346 AC: 204132 AN: 590536 Hom.: 36578 AF XY: 0.343 AC XY: 107958 AN XY: 314494

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.527

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.327

GnomAD4 genome AF: 0.304 AC: 46112 AN: 151900 Hom.: 7746 Cov.: 32 AF XY: 0.307 AC XY: 22787 AN XY: 74220

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.309

Alfa AF: 0.325 Hom.: 1997

Bravo AF: 0.306

Asia WGS AF: 0.270 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.013
DANN	Benign	0.62

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: rs13109660; hg19: chr4-55970680; COSMIC: COSV55757296; COSMIC: COSV55757296;