4-55083995-A-G

Variant names:

• chr4-55083995-A-G
• rs10434442
• NM_002253.4:c.3663-1360T>C

Variant summary

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

The NM_002253.4(KDR):​c.3663-1360T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,128 control chromosomes in the GnomAD database, including 7,462 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 0.28 (7462 hom., cov: 32)
• Consequence: KDR NM_002253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.88
• Publications: 2 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

ENSG00000250646 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4	c.3663-1360T>C		intron_variant	Intron 27 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDR	ENST00000263923.5	c.3663-1360T>C		intron_variant	Intron 27 of 29	1	NM_002253.4	ENSP00000263923.4
ENSG00000250646	ENST00000511222.1	n.234-8318A>G		intron_variant	Intron 3 of 3	5
KDR	ENST00000647068.1	n.3676-1360T>C		intron_variant	Intron 27 of 29

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42625 AN: 152010 Hom.: 7437 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.281 AC: 42696 AN: 152128 Hom.: 7462 Cov.: 32 AF XY: 0.277 AC XY: 20620 AN XY: 74372

African (AFR) AF: 0.494 AC: 20479 AN: 41490

American (AMR) AF: 0.194 AC: 2958 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3466

East Asian (EAS) AF: 0.148 AC: 766 AN: 5164

South Asian (SAS) AF: 0.215 AC: 1039 AN: 4830

European-Finnish (FIN) AF: 0.188 AC: 1991 AN: 10600

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13434 AN: 67984

Other (OTH) AF: 0.274 AC: 578 AN: 2112

Alfa AF: 0.133 Hom.: 236

Bravo AF: 0.288

Asia WGS AF: 0.219 AC: 763 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	0.011
DANN	Benign	0.19
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10434442; hg19: chr4-55950162;