rs246391

Positions:

chr5-150117614-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002609.4(PDGFRB):c.3137+4A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,557,850 control chromosomes in the GnomAD database, including 131,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11108 hom., cov: 30)

Exomes 𝑓: 0.41 ( 120262 hom. )

Consequence

PDGFRB
NM_002609.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.08385

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.430

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 5-150117614-T-C is Benign according to our data. Variant chr5-150117614-T-C is described in ClinVar as [Benign]. Clinvar id is 258778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150117614-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
PDGFRB	NM_002609.4 linkuse as main transcript	c.3137+4A>G	splice_donor_region_variant, intron_variant	ENST00000261799.9	NP_002600.1
PDGFRB	NM_001355016.2 linkuse as main transcript	c.2945+4A>G	splice_donor_region_variant, intron_variant		NP_001341945.1
PDGFRB	NM_001355017.2 linkuse as main transcript	c.2654+4A>G	splice_donor_region_variant, intron_variant		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9 linkuse as main transcript	c.3137+4A>G		splice_donor_region_variant, intron_variant		1	NM_002609.4	ENSP00000261799	P1	P09619-1
PDGFRB	ENST00000520579.5 linkuse as main transcript	c.*2451+4A>G		splice_donor_region_variant, intron_variant, NMD_transcript_variant		1		ENSP00000430026

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

56810

AN:

150874

Hom.:

11093

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.434

Gnomad OTH

AF:

0.391

GnomAD3 exomes

AF:

0.348

AC:

86283

AN:

248036

Hom.:

16475

AF XY:

0.354

AC XY:

47476

AN XY:

134070

show subpopulations

Gnomad AFR exome

AF:

0.353

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.455

Gnomad EAS exome

AF:

0.114

Gnomad SAS exome

AF:

0.330

Gnomad FIN exome

AF:

0.241

Gnomad NFE exome

AF:

0.430

Gnomad OTH exome

AF:

0.373

GnomAD4 exome

AF:

0.406

AC:

570893

AN:

1406860

Hom.:

120262

Cov.:

AF XY:

0.404

AC XY:

283603

AN XY:

701714

show subpopulations

Gnomad4 AFR exome

AF:

0.351

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.458

Gnomad4 EAS exome

AF:

0.121

Gnomad4 SAS exome

AF:

0.329

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.437

Gnomad4 OTH exome

AF:

0.399

GnomAD4 genome

AF:

0.377

AC:

56855

AN:

150990

Hom.:

11108

Cov.:

AF XY:

0.365

AC XY:

26923

AN XY:

73696

show subpopulations

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.347

Gnomad4 ASJ

AF:

0.463

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.328

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.434

Gnomad4 OTH

AF:

0.391

Alfa

AF:

0.421

Hom.:

20775

Bravo

AF:

0.378

Asia WGS

AF:

0.226

AC:

784

AN:

3476

EpiCase

AF:

0.436

EpiControl

AF:

0.440

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Acroosteolysis-keloid-like lesions-premature aging syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Basal ganglia calcification, idiopathic, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Myeloproliferative disorder, chronic, with eosinophilia

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.2

DANN

Benign

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.084

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over