rs11941492

Variant names:

• chr4-55112043-C-T
• rs11941492
• NM_002253.4:c.976+1261G>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+1261G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,044 control chromosomes in the GnomAD database, including 4,792 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 0.25 (4792 hom., cov: 33)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 20 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.976+1261G>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+1261G>A		intron_variant	Intron 7 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000512566.1	n.976+1261G>A		intron_variant	Intron 7 of 12	1
KDR	ENST00000647068.1	n.989+1261G>A		intron_variant	Intron 7 of 29

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37383 AN: 151926 Hom.: 4787 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.246 AC: 37409 AN: 152044 Hom.: 4792 Cov.: 33 AF XY: 0.246 AC XY: 18252 AN XY: 74328

African (AFR) AF: 0.276 AC: 11439 AN: 41448

American (AMR) AF: 0.221 AC: 3373 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1236 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1549 AN: 5178

South Asian (SAS) AF: 0.437 AC: 2102 AN: 4810

European-Finnish (FIN) AF: 0.174 AC: 1842 AN: 10556

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15110 AN: 67986

Other (OTH) AF: 0.250 AC: 526 AN: 2108

Alfa AF: 0.241 Hom.: 5671

Bravo AF: 0.247

Asia WGS AF: 0.349 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.54
PhyloP100		-1.2
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: rs11941492; hg19: chr4-55978210;