NM_002609.4:c.3137+4A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002609.4(PDGFRB):c.3137+4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,557,850 control chromosomes in the GnomAD database, including 131,370 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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_region, intron

Scores

Splicing: ADA: 0.08385

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.430

Publications

24 publications found

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 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

PDGFRB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar 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 CliVar as Benign. Clinvar id is 258778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDGFRB	NM_002609.4 link	c.3137+4A>G	splice_region_variant, intron_variant	Intron 22 of 22	ENST00000261799.9	NP_002600.1	P09619-1Q59F04
PDGFRB	NM_001355016.2 link	c.2945+4A>G	splice_region_variant, intron_variant	Intron 21 of 21		NP_001341945.1
PDGFRB	NM_001355017.2 link	c.2654+4A>G	splice_region_variant, intron_variant	Intron 22 of 22		NP_001341946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRB	ENST00000261799.9 link	c.3137+4A>G		splice_region_variant, intron_variant	Intron 22 of 22	1	NM_002609.4	ENSP00000261799.4		P09619-1
PDGFRB	ENST00000520579.5 link	n.*2451+4A>G		splice_region_variant, intron_variant	Intron 22 of 22	1		ENSP00000430026.1		E5RH16

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

GnomAD2 exomes

AF:

0.348

AC:

86283

AN:

248036

AF XY:

0.354

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 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

African (AFR)

AF:

0.351

AC:

11350

AN:

32336

American (AMR)

AF:

0.259

AC:

11524

AN:

44450

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

11732

AN:

25638

East Asian (EAS)

AF:

0.121

AC:

4764

AN:

39218

South Asian (SAS)

AF:

0.329

AC:

27910

AN:

84846

European-Finnish (FIN)

AF:

0.250

AC:

13276

AN:

53210

Middle Eastern (MID)

AF:

0.457

AC:

2519

AN:

5512

European-Non Finnish (NFE)

AF:

0.437

AC:

464499

AN:

1063214

Other (OTH)

AF:

0.399

AC:

23319

AN:

58436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

16108

32215

48323

64430

80538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13732

27464

41196

54928

68660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.377

AC:

56855

AN:

150990

Hom.:

11108

Cov.:

AF XY:

0.365

AC XY:

26923

AN XY:

73696

show subpopulations

African (AFR)

AF:

0.357

AC:

14675

AN:

41086

American (AMR)

AF:

0.347

AC:

5271

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1604

AN:

3468

East Asian (EAS)

AF:

0.114

AC:

572

AN:

5024

South Asian (SAS)

AF:

0.328

AC:

1561

AN:

4756

European-Finnish (FIN)

AF:

0.237

AC:

2451

AN:

10320

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.434

AC:

29418

AN:

67828

Other (OTH)

AF:

0.391

AC:

820

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1709

3419

5128

6838

8547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.420

Hom.:

25799

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:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Acroosteolysis-keloid-like lesions-premature aging syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Basal ganglia calcification, idiopathic, 4

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not provided

Benign:1

Jan 10, 2019

GeneDx

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

Feb 03, 2025

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

-0.84

CADD

Benign

9.2

(source)

DANN

Benign

0.34

PhyloP100

-0.43

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over