chr5-150126061-T-C

Variant names:

• chr5-150126061-T-C
• rs3756309
• NM_002609.4:c.1674+459A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

PDGFRB Gene-Disease associations (from GenCC):

• acroosteolysis-keloid-like lesions-premature aging syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• myofibromatosis, infantile, 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• basal ganglia calcification, idiopathic, 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile myofibromatosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary progressive mucinous histiocytosis

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002609.4. 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
	PDGFRB	NM_002609.4	MANE Select	c.1674+459A>G		intron	N/A	NP_002600.1	P09619-1
	PDGFRB	NM_001355016.2		c.1482+459A>G		intron	N/A	NP_001341945.1
	PDGFRB	NM_001355017.2		c.1191+459A>G		intron	N/A	NP_001341946.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRB	ENST00000261799.9	TSL:1 MANE Select	c.1674+459A>G		intron	N/A	ENSP00000261799.4	P09619-1
	PDGFRB	ENST00000520579.5	TSL:1	n.*988+459A>G		intron	N/A	ENSP00000430026.1	E5RH16
	PDGFRB	ENST00000890716.1		c.1674+459A>G		intron	N/A	ENSP00000560775.1

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

African (AFR) AF: 0.267 AC: 11099 AN: 41504

American (AMR) AF: 0.318 AC: 4860 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3472

East Asian (EAS) AF: 0.169 AC: 875 AN: 5190

South Asian (SAS) AF: 0.344 AC: 1658 AN: 4822

European-Finnish (FIN) AF: 0.225 AC: 2381 AN: 10580

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20300 AN: 67998

Other (OTH) AF: 0.290 AC: 614 AN: 2114

Alfa AF: 0.295 Hom.: 27416

Bravo AF: 0.286

Asia WGS AF: 0.291 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.84
PhyloP100		-0.65
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: rs3756309; hg19: chr5-149505624; COSMIC: COSV55800055;