5-150125491-C-T

Position:

• chr5-150125491-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_002609.4(PDGFRB):​c.1761G>A​(p.Leu587=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,613,466 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0087 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (13 hom.)
• Consequence: PDGFRB NM_002609.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.35

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 5-150125491-C-T is Benign according to our data. Variant chr5-150125491-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 540602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150125491-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.36 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00865 (1318/152306) while in subpopulation AFR AF= 0.0291 (1209/41566). AF 95% confidence interval is 0.0277. There are 17 homozygotes in gnomad4. There are 642 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1318 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDGFRB	NM_002609.4	c.1761G>A	p.Leu587=	synonymous_variant	12/23	ENST00000261799.9
PDGFRB	NM_001355016.2	c.1569G>A	p.Leu523=	synonymous_variant	11/22
PDGFRB	NM_001355017.2	c.1278G>A	p.Leu426=	synonymous_variant	12/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDGFRB	ENST00000261799.9	c.1761G>A	p.Leu587=	synonymous_variant	12/23	1	NM_002609.4	P1
PDGFRB	ENST00000520579.5	c.*1075G>A		3_prime_UTR_variant, NMD_transcript_variant	12/23	1
PDGFRB	ENST00000520229.1	n.30G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.00867 AC: 1320 AN: 152188 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00222 AC: 557 AN: 251294 Hom.: 8 AF XY: 0.00165 AC XY: 224 AN XY: 135810

Gnomad AFR exome AF: 0.0276

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000981

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00100 AC: 1463 AN: 1461160 Hom.: 13 Cov.: 31 AF XY: 0.000885 AC XY: 643 AN XY: 726932

Gnomad4 AFR exome AF: 0.0298

Gnomad4 AMR exome AF: 0.00201

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000178

Gnomad4 OTH exome AF: 0.00229

GnomAD4 genome AF: 0.00865 AC: 1318 AN: 152306 Hom.: 17 Cov.: 32 AF XY: 0.00862 AC XY: 642 AN XY: 74468

Gnomad4 AFR AF: 0.0291

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00401 Hom.: 0

Bravo AF: 0.00984

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2019

- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	12
DANN	Benign	0.76

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: rs56078873; hg19: chr5-149505054;