chr5-150156062-A-C

Variant names:

• chr5-150156062-A-C
• rs3828610
• NM_002609.4:c.-672T>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.-672T>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 150,962 control chromosomes in the GnomAD database, including 19,661 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 0.49 (19661 hom., cov: 31)
• Consequence: PDGFRB NM_002609.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445
• Publications: 15 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• basal ganglia calcification, idiopathic, 4

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4	c.-672T>G		upstream_gene_variant		ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2	c.-818T>G		upstream_gene_variant			NP_001341945.1
PDGFRB	NM_001355017.2	c.-1189T>G		upstream_gene_variant			NP_001341946.1
PDGFRB	NR_149150.2	n.-217T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9	c.-672T>G		upstream_gene_variant		1	NM_002609.4	ENSP00000261799.4
PDGFRB	ENST00000520579.5	n.-672T>G		upstream_gene_variant		1		ENSP00000430026.1
PDGFRB	ENST00000517660.1	n.-202T>G		upstream_gene_variant		3
PDGFRB	ENST00000523456.1	n.-190T>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73479 AN: 150848 Hom.: 19619 Cov.: 31

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.487 AC: 73587 AN: 150962 Hom.: 19661 Cov.: 31 AF XY: 0.484 AC XY: 35696 AN XY: 73684

African (AFR) AF: 0.720 AC: 29715 AN: 41286

American (AMR) AF: 0.450 AC: 6836 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1918 AN: 3468

East Asian (EAS) AF: 0.579 AC: 2959 AN: 5110

South Asian (SAS) AF: 0.402 AC: 1914 AN: 4758

European-Finnish (FIN) AF: 0.337 AC: 3480 AN: 10324

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25270 AN: 67550

Other (OTH) AF: 0.495 AC: 1035 AN: 2090

Alfa AF: 0.443 Hom.: 2646

Bravo AF: 0.506

Asia WGS AF: 0.491 AC: 1707 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.85
PhyloP100		0.45
PromoterAI		0.0070	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3828610; hg19: chr5-149535625;