rs6837735

Variant names:

• chr4-55119648-C-T
• rs6837735
• NM_002253.4:c.162-848G>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.162-848G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,928 control chromosomes in the GnomAD database, including 3,482 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 0.20 (3482 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002253.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	NM_002253.4	MANE Select	c.162-848G>A		intron	N/A	NP_002244.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDR	ENST00000263923.5	TSL:1 MANE Select	c.162-848G>A		intron	N/A	ENSP00000263923.4
	KDR	ENST00000512566.1	TSL:1	n.162-848G>A		intron	N/A
	KDR	ENST00000922964.1		c.162-848G>A		intron	N/A	ENSP00000593023.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30995 AN: 151810 Hom.: 3480 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.204 AC: 31019 AN: 151928 Hom.: 3482 Cov.: 32 AF XY: 0.212 AC XY: 15751 AN XY: 74244

African (AFR) AF: 0.173 AC: 7161 AN: 41420

American (AMR) AF: 0.199 AC: 3032 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2288 AN: 5160

South Asian (SAS) AF: 0.367 AC: 1766 AN: 4806

European-Finnish (FIN) AF: 0.273 AC: 2876 AN: 10518

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12687 AN: 67964

Other (OTH) AF: 0.200 AC: 423 AN: 2110

Alfa AF: 0.195 Hom.: 12248

Bravo AF: 0.194

Asia WGS AF: 0.391 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.30
PhyloP100		-0.29
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: rs6837735; hg19: chr4-55985815;