4-55096165-C-T

Variant summary

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

The NM_002253.4(KDR):c.2728+64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 881,008 control chromosomes in the GnomAD database, including 50 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 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (20 hom.)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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=-0.8).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1800/152274) while in subpopulation AFR AF= 0.0416 (1727/41560). AF 95% confidence interval is 0.0399. There are 30 homozygotes in gnomad4. There are 862 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1784 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDR	NM_002253.4	c.2728+64G>A		intron_variant		ENST00000263923.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDR	ENST00000263923.5	c.2728+64G>A		intron_variant		1	NM_002253.4	P1
KDR	ENST00000509309.1	n.492+64G>A		intron_variant, non_coding_transcript_variant		3
KDR	ENST00000647068.1	n.2741+64G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1784 AN: 152156 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.00147 AC: 1071 AN: 728734 Hom.: 20 AF XY: 0.00115 AC XY: 447 AN XY: 389986

Gnomad4 AFR exome AF: 0.0442

Gnomad4 AMR exome AF: 0.00172

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000424

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000506

Gnomad4 OTH exome AF: 0.00275

GnomAD4 genome AF: 0.0118 AC: 1800 AN: 152274 Hom.: 30 Cov.: 32 AF XY: 0.0116 AC XY: 862 AN XY: 74460

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.000281 Hom.: 0

Bravo AF: 0.0128

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	14
Dann	Benign	0.65

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: rs17085274; hg19: chr4-55962332;