chr5-150135020-C-A

Variant names:

• chr5-150135020-C-A
• rs139448702
• NM_002609.4:c.365-4G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002609.4(PDGFRB):​c.365-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,473,394 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (11 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (6 hom.)
• Consequence: PDGFRB NM_002609.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002909
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.251
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 5-150135020-C-A is Benign according to our data. Variant chr5-150135020-C-A is described in ClinVar as [Benign]. Clinvar id is 473407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00536 (816/152288) while in subpopulation AFR AF = 0.0189 (786/41558). AF 95% confidence interval is 0.0178. There are 11 homozygotes in GnomAd4. There are 361 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 816 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4	c.365-4G>T		splice_region_variant, intron_variant	Intron 3 of 22	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2	c.173-4G>T		splice_region_variant, intron_variant	Intron 2 of 21		NP_001341945.1
PDGFRB	NM_001355017.2	c.-153-4G>T		splice_region_variant, intron_variant	Intron 3 of 22		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9	c.365-4G>T		splice_region_variant, intron_variant	Intron 3 of 22	1	NM_002609.4	ENSP00000261799.4
PDGFRB	ENST00000520579.5	n.365-4G>T		splice_region_variant, intron_variant	Intron 3 of 22	1		ENSP00000430026.1
PDGFRB	ENST00000517957.1	c.365-4G>T		splice_region_variant, intron_variant	Intron 3 of 3	4		ENSP00000430715.1
PDGFRB	ENST00000517488.1	c.173-4G>T		splice_region_variant, intron_variant	Intron 2 of 2	3		ENSP00000429218.1

Frequencies

GnomAD3 genomes AF: 0.00536 AC: 815 AN: 152170 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.00146 AC: 340 AN: 233422 AF XY: 0.000990

Gnomad AFR exome AF: 0.0191

Gnomad AMR exome AF: 0.000844

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.000882

GnomAD4 exome AF: 0.000532 AC: 703 AN: 1321106 Hom.: 6 Cov.: 20 AF XY: 0.000478 AC XY: 316 AN XY: 661036

African (AFR) AF: 0.0189 AC: 581 AN: 30694

American (AMR) AF: 0.000882 AC: 38 AN: 43084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23996

East Asian (EAS) AF: 0.00 AC: 0 AN: 38934

South Asian (SAS) AF: 0.0000250 AC: 2 AN: 80104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52532

Middle Eastern (MID) AF: 0.00119 AC: 5 AN: 4188

European-Non Finnish (NFE) AF: 0.0000141 AC: 14 AN: 992072

Other (OTH) AF: 0.00114 AC: 63 AN: 55502

GnomAD4 genome AF: 0.00536 AC: 816 AN: 152288 Hom.: 11 Cov.: 33 AF XY: 0.00485 AC XY: 361 AN XY: 74472

African (AFR) AF: 0.0189 AC: 786 AN: 41558

American (AMR) AF: 0.00144 AC: 22 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00381 Hom.: 1

Bravo AF: 0.00609

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Myofibromatosis, infantile, 1 Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Myeloproliferative disorder, chronic, with eosinophilia Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Infantile myofibromatosis;C1866182:Acroosteolysis-keloid-like lesions-premature aging syndrome;C3554321:Basal ganglia calcification, idiopathic, 4;C4225270:Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome Benign:1

Nov 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.5
DANN	Benign	0.71
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.078
SpliceAI score (max)		0.040		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: rs139448702; hg19: chr5-149514583;