4-55124875-G-T

Variant names:

• chr4-55124875-G-T
• rs12502008
• NM_002253.4:c.67+352C>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.67+352C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,950 control chromosomes in the GnomAD database, including 9,742 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 0.34 (9742 hom., cov: 31)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 16 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.67+352C>A		intron_variant	Intron 1 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.67+352C>A		intron_variant	Intron 1 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000512566.1	n.67+352C>A		intron_variant	Intron 1 of 12	1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52354 AN: 151832 Hom.: 9722 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.345 AC: 52412 AN: 151950 Hom.: 9742 Cov.: 31 AF XY: 0.348 AC XY: 25864 AN XY: 74242

African (AFR) AF: 0.237 AC: 9822 AN: 41454

American (AMR) AF: 0.471 AC: 7201 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3472

East Asian (EAS) AF: 0.585 AC: 2992 AN: 5118

South Asian (SAS) AF: 0.378 AC: 1819 AN: 4814

European-Finnish (FIN) AF: 0.374 AC: 3946 AN: 10558

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24381 AN: 67942

Other (OTH) AF: 0.358 AC: 757 AN: 2114

Alfa AF: 0.346 Hom.: 11490

Bravo AF: 0.350

Asia WGS AF: 0.488 AC: 1695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.76
PhyloP100		-0.078
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: rs12502008; hg19: chr4-55991042;