chr4-54258424-A-G

Position:

• chr4-54258424-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006206.6(PDGFRA):​c.-12-333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,010 control chromosomes in the GnomAD database, including 4,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4905 hom., cov: 32)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.47

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 4-54258424-A-G is Benign according to our data. Variant chr4-54258424-A-G is described in ClinVar as [Benign]. Clinvar id is 1263122.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.-12-333A>G		intron_variant		ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.-12-333A>G		intron_variant		1	NM_006206.6	ENSP00000257290	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34878 AN: 151892 Hom.: 4895 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 34933 AN: 152010 Hom.: 4905 Cov.: 32 AF XY: 0.231 AC XY: 17160 AN XY: 74322

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.199

Alfa AF: 0.188 Hom.: 411

Bravo AF: 0.248

Asia WGS AF: 0.259 AC: 901 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.0
DANN	Benign	0.91

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

Other links and lift over

dbSNP: rs9991165; hg19: chr4-55124591;