4-55112903-C-T

Variant names:

• chr4-55112903-C-T
• rs10020464
• NM_002253.4:c.976+401G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002253.4(KDR):​c.976+401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,034 control chromosomes in the GnomAD database, including 8,684 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 0.33 (8684 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• Publications: 14 publications found

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]

KDR Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.976+401G>A		intron_variant	Intron 7 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.976+401G>A		intron_variant	Intron 7 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000512566.1	n.976+401G>A		intron_variant	Intron 7 of 12	1
KDR	ENST00000647068.1	n.989+401G>A		intron_variant	Intron 7 of 29

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50330 AN: 151916 Hom.: 8683 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.331 AC: 50352 AN: 152034 Hom.: 8684 Cov.: 32 AF XY: 0.335 AC XY: 24906 AN XY: 74342

African (AFR) AF: 0.354 AC: 14690 AN: 41480

American (AMR) AF: 0.279 AC: 4270 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1126 AN: 3470

East Asian (EAS) AF: 0.595 AC: 3058 AN: 5138

South Asian (SAS) AF: 0.540 AC: 2601 AN: 4820

European-Finnish (FIN) AF: 0.314 AC: 3319 AN: 10572

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20277 AN: 67956

Other (OTH) AF: 0.326 AC: 687 AN: 2108

Alfa AF: 0.306 Hom.: 3681

Bravo AF: 0.325

Asia WGS AF: 0.561 AC: 1950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.77
DANN	Benign	0.19
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10020464; hg19: chr4-55979070;