rs55634318

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002608.4(PDGFB):c.453C>G(p.Val151Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,562,296 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 51 hom., cov: 32)

Exomes 𝑓: 0.013 ( 125 hom. )

Consequence

PDGFB
NM_002608.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.632

Publications

5 publications found

Variant links:

Genes affected

PDGFB (HGNC:8800): (platelet derived growth factor subunit B) This gene encodes a member of the protein family comprised of both platelet-derived growth factors (PDGF) and vascular endothelial growth factors (VEGF). The encoded preproprotein is proteolytically processed to generate platelet-derived growth factor subunit B, which can homodimerize, or alternatively, heterodimerize with the related platelet-derived growth factor subunit A. These proteins bind and activate PDGF receptor tyrosine kinases, which play a role in a wide range of developmental processes. Mutations in this gene are associated with meningioma. Reciprocal translocations between chromosomes 22 and 17, at sites where this gene and that for collagen type 1, alpha 1 are located, are associated with dermatofibrosarcoma protuberans, a rare skin tumor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

PDGFB Gene-Disease associations (from GenCC):

basal ganglia calcification, idiopathic, 5
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
bilateral striopallidodentate calcinosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial meningioma
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

PDGFB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 22-39231625-G-C is Benign according to our data. Variant chr22-39231625-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1188397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.632 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0197 (3008/152310) while in subpopulation AFR AF = 0.0385 (1601/41570). AF 95% confidence interval is 0.0369. There are 51 homozygotes in GnomAd4. There are 1455 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3008 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFB	NM_002608.4 link	c.453C>G	p.Val151Val	synonymous_variant	Exon 4 of 7	ENST00000331163.11	NP_002599.1	P01127-1A0A384NYY3
PDGFB	NM_033016.3 link	c.408C>G	p.Val136Val	synonymous_variant	Exon 4 of 7		NP_148937.1	P01127-2
PDGFB	XM_047441393.1 link	c.360C>G	p.Val120Val	synonymous_variant	Exon 4 of 7		XP_047297349.1
PDGFB	XM_047441394.1 link	c.360C>G	p.Val120Val	synonymous_variant	Exon 4 of 7		XP_047297350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDGFB	ENST00000331163.11 link	c.453C>G	p.Val151Val	synonymous_variant	Exon 4 of 7	1	NM_002608.4	ENSP00000330382.6	P01127-1
PDGFB	ENST00000381551.8 link	c.408C>G	p.Val136Val	synonymous_variant	Exon 4 of 7	5		ENSP00000370963.4	P01127-2
PDGFB	ENST00000455790.5 link	c.360C>G	p.Val120Val	synonymous_variant	Exon 4 of 5	4		ENSP00000402306.1	A9UJP0
PDGFB	ENST00000440375.1 link	c.360C>G	p.Val120Val	synonymous_variant	Exon 4 of 5	4		ENSP00000405780.1	A9UJN9

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2978

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0379

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.0188

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0117

AC:

2011

AN:

171928

AF XY:

0.0114

show subpopulations

Gnomad AFR exome

AF:

0.0352

Gnomad AMR exome

AF:

0.00935

Gnomad ASJ exome

AF:

0.00712

Gnomad EAS exome

AF:

0.000227

Gnomad FIN exome

AF:

0.00448

Gnomad NFE exome

AF:

0.0123

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0130

AC:

18377

AN:

1409986

Hom.:

125

Cov.:

AF XY:

0.0130

AC XY:

9050

AN XY:

697104

show subpopulations

African (AFR)

AF:

0.0378

AC:

1224

AN:

32384

American (AMR)

AF:

0.0107

AC:

402

AN:

37708

Ashkenazi Jewish (ASJ)

AF:

0.00771

AC:

194

AN:

25172

East Asian (EAS)

AF:

0.0000808

AC:

AN:

37132

South Asian (SAS)

AF:

0.0161

AC:

1293

AN:

80362

European-Finnish (FIN)

AF:

0.00476

AC:

224

AN:

47058

Middle Eastern (MID)

AF:

0.0166

AC:

AN:

4768

European-Non Finnish (NFE)

AF:

0.0130

AC:

14095

AN:

1086918

Other (OTH)

AF:

0.0148

AC:

863

AN:

58484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

928

1857

2785

3714

4642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.0197

AC:

3008

AN:

152310

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

1455

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0385

AC:

1601

AN:

41570

American (AMR)

AF:

0.0188

AC:

287

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0143

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00339

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0133

AC:

907

AN:

68016

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

140

279

419

558

698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0147

Hom.:

Bravo

AF:

0.0212

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 01, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Genome Diagnostics Laboratory, Amsterdam University 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

- -

PDGFB-related disorder

Benign:1

Nov 12, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

(source)

DANN

Benign

0.63

PhyloP100

-0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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