rs3756309

chr5-150126061-T-C

Variant summary

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

The NM_002609.4(PDGFRB):c.1674+459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,178 control chromosomes in the GnomAD database, including 6,293 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 (6293 hom., cov: 32)
• Consequence: PDGFRB NM_002609.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRB	NM_002609.4	c.1674+459A>G		intron_variant		ENST00000261799.9
PDGFRB	NM_001355016.2	c.1482+459A>G		intron_variant
PDGFRB	NM_001355017.2	c.1191+459A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9	c.1674+459A>G		intron_variant		1	NM_002609.4	P1
PDGFRB	ENST00000520579.5	c.*988+459A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43283 AN: 152060 Hom.: 6267 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.285 AC: 43360 AN: 152178 Hom.: 6293 Cov.: 32 AF XY: 0.282 AC XY: 21005 AN XY: 74398

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.290

Alfa AF: 0.298 Hom.: 13576

Bravo AF: 0.286

Asia WGS AF: 0.291 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.9
Dann	Benign	0.84

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: rs3756309; hg19: chr5-149505624; COSMIC: COSV55800055; COSMIC: COSV55800055;