chr4-54229547-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006206.6(PDGFRA):​c.-13+132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 390,056 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 8 hom., cov: 31)
Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

PDGFRA
NM_006206.6 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.168
Variant links:
Genes affected
PDGFRA (HGNC:8803): (platelet derived growth factor receptor alpha) This gene encodes 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 or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers. [provided by RefSeq, Mar 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 4-54229547-T-G is Benign according to our data. Variant chr4-54229547-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1302476.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00691 (1041/150584) while in subpopulation AFR AF= 0.0239 (981/41126). AF 95% confidence interval is 0.0226. There are 8 homozygotes in gnomad4. There are 501 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1041 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PDGFRANM_006206.6 linkuse as main transcriptc.-13+132T>G intron_variant ENST00000257290.10 NP_006197.1
PDGFRANM_001347827.2 linkuse as main transcriptc.-13+132T>G intron_variant NP_001334756.1
PDGFRANM_001347828.2 linkuse as main transcriptc.-16+132T>G intron_variant NP_001334757.1
PDGFRAXM_006714041.4 linkuse as main transcriptc.-16+132T>G intron_variant XP_006714104.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PDGFRAENST00000257290.10 linkuse as main transcriptc.-13+132T>G intron_variant 1 NM_006206.6 ENSP00000257290 P1P16234-1

Frequencies

GnomAD3 genomes
AF:
0.00692
AC:
1042
AN:
150520
Hom.:
8
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0239
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00252
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000623
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00433
GnomAD4 exome
AF:
0.00101
AC:
242
AN:
239472
Hom.:
3
AF XY:
0.000913
AC XY:
111
AN XY:
121524
show subpopulations
Gnomad4 AFR exome
AF:
0.0247
Gnomad4 AMR exome
AF:
0.00248
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000971
Gnomad4 OTH exome
AF:
0.00214
GnomAD4 genome
AF:
0.00691
AC:
1041
AN:
150584
Hom.:
8
Cov.:
31
AF XY:
0.00682
AC XY:
501
AN XY:
73462
show subpopulations
Gnomad4 AFR
AF:
0.0239
Gnomad4 AMR
AF:
0.00251
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000417
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00429
Alfa
AF:
0.00576
Hom.:
2
Bravo
AF:
0.00796
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxApr 01, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
12
DANN
Benign
0.60

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

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

Other links and lift over

dbSNP: rs74962312; hg19: chr4-55095714; API