rs17708574

Positions:

• chr5-150141675-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002609.4(PDGFRB):​c.-6-4622C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 152,224 control chromosomes in the GnomAD database, including 736 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 0.085 (736 hom., cov: 32)
• Consequence: PDGFRB NM_002609.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943

Genes affected

PDGFRB (HGNC:8804): (platelet derived growth factor receptor beta) The protein encoded by this gene is a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer (PDGFB or PDGFD) or a heterodimer (PDGFA and PDGFB). This gene is essential for normal development of the cardiovascular system and aids in rearrangement of the actin cytoskeleton. This gene is flanked on chromosome 5 by the genes for granulocyte-macrophage colony-stimulating factor and macrophage-colony stimulating factor receptor; all three genes may be implicated in the 5-q syndrome. A translocation between chromosomes 5 and 12, that fuses this gene to that of the ETV6 gene, results in chronic myeloproliferative disorder with eosinophilia. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRB	NM_002609.4	c.-6-4622C>T		intron_variant		ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2	c.-152-5797C>T		intron_variant			NP_001341945.1
PDGFRB	NM_001355017.2	c.-523-4622C>T		intron_variant			NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9	c.-6-4622C>T		intron_variant		1	NM_002609.4	ENSP00000261799	P1
PDGFRB	ENST00000520579.5	c.-6-4622C>T		intron_variant, NMD_transcript_variant		1		ENSP00000430026
PDGFRB	ENST00000517488.1	c.-152-5797C>T		intron_variant		3		ENSP00000429218
PDGFRB	ENST00000517660.1	n.465-4225C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12960 AN: 152106 Hom.: 738 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0976

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

GnomAD4 genome AF: 0.0851 AC: 12957 AN: 152224 Hom.: 736 Cov.: 32 AF XY: 0.0871 AC XY: 6482 AN XY: 74414

Gnomad4 AFR AF: 0.0215

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.0769

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0990

Alfa AF: 0.106 Hom.: 1178

Bravo AF: 0.0825

Asia WGS AF: 0.175 AC: 608 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.9
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs17708574; hg19: chr5-149521238;