rs758588

Variant names:

• chr5-150155167-G-A
• rs758588
• NM_002609.4:c.-7+230C>T

Variant summary

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

The NM_002609.4(PDGFRB):​c.-7+230C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,158 control chromosomes in the GnomAD database, including 2,316 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 0.15 (2316 hom., cov: 31)
• Consequence: PDGFRB NM_002609.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 6 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=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4	c.-7+230C>T		intron_variant	Intron 1 of 22	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2	c.-153+230C>T		intron_variant	Intron 1 of 21		NP_001341945.1
PDGFRB	NM_001355017.2	c.-524+230C>T		intron_variant	Intron 1 of 22		NP_001341946.1
PDGFRB	NR_149150.2	n.449+230C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9	c.-7+230C>T		intron_variant	Intron 1 of 22	1	NM_002609.4	ENSP00000261799.4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23525 AN: 152040 Hom.: 2316 Cov.: 31

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.155 AC: 23527 AN: 152158 Hom.: 2316 Cov.: 31 AF XY: 0.151 AC XY: 11239 AN XY: 74382

African (AFR) AF: 0.0450 AC: 1870 AN: 41538

American (AMR) AF: 0.186 AC: 2838 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3470

East Asian (EAS) AF: 0.132 AC: 680 AN: 5160

South Asian (SAS) AF: 0.118 AC: 571 AN: 4820

European-Finnish (FIN) AF: 0.143 AC: 1520 AN: 10600

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14270 AN: 67992

Other (OTH) AF: 0.201 AC: 424 AN: 2112

Alfa AF: 0.170 Hom.: 304

Bravo AF: 0.154

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.4
DANN	Benign	0.87
PhyloP100		0.23
PromoterAI		0.020	Neutral
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: rs758588; hg19: chr5-149534730;