chr5-150135020-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

2
Splicing: ADA: 0.0002909
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.251

Publications

0 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

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=-0.68).
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
PDGFRBNM_002609.4 linkc.365-4G>T splice_region_variant, intron_variant Intron 3 of 22 ENST00000261799.9 NP_002600.1 P09619-1Q59F04
PDGFRBNM_001355016.2 linkc.173-4G>T splice_region_variant, intron_variant Intron 2 of 21 NP_001341945.1
PDGFRBNM_001355017.2 linkc.-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
PDGFRBENST00000261799.9 linkc.365-4G>T splice_region_variant, intron_variant Intron 3 of 22 1 NM_002609.4 ENSP00000261799.4 P09619-1
PDGFRBENST00000520579.5 linkn.365-4G>T splice_region_variant, intron_variant Intron 3 of 22 1 ENSP00000430026.1 E5RH16
PDGFRBENST00000517957.1 linkc.365-4G>T splice_region_variant, intron_variant Intron 3 of 3 4 ENSP00000430715.1 E5RII0
PDGFRBENST00000517488.1 linkc.173-4G>T splice_region_variant, intron_variant Intron 2 of 2 3 ENSP00000429218.1 E5RJ14

Frequencies

GnomAD3 genomes
AF:
0.00536
AC:
815
AN:
152170
Hom.:
10
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
37
74
110
147
184
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.00536
AC:
816
AN:
152288
Hom.:
11
Cov.:
33
AF XY:
0.00485
AC XY:
361
AN XY:
74472
show subpopulations
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
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
39
78
116
155
194
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00381
Hom.:
1
Bravo
AF:
0.00609

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

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

Publications

Other links and lift over

dbSNP: rs139448702; hg19: chr5-149514583; API