4-54295087-C-T

Variant names:

• chr4-54295087-C-T
• rs3733540
• NM_006206.6:c.3123-38C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001347828.2(PDGFRA):​c.3198-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,598,460 control chromosomes in the GnomAD database, including 560,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (44288 hom., cov: 32)
  • Exomes 𝑓: 0.84 (515955 hom.)
• Consequence: PDGFRA NM_001347828.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.817
• Publications: 16 publications found

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]

PDGFRA Gene-Disease associations (from GenCC):

• gastrointestinal stromal tumor

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• polyps, multiple and recurrent inflammatory fibroid, gastrointestinal

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, G2P
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• isolated cleft palate

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000282278 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-54295087-C-T is Benign according to our data. Variant chr4-54295087-C-T is described in ClinVar as Benign. ClinVar VariationId is 259952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347828.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	NM_006206.6	MANE Select	c.3123-38C>T		intron	N/A	NP_006197.1
	PDGFRA	NM_001347828.2		c.3198-38C>T		intron	N/A	NP_001334757.1
	PDGFRA	NM_001347830.2		c.3162-38C>T		intron	N/A	NP_001334759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.3123-38C>T		intron	N/A	ENSP00000257290.5
	ENSG00000282278	ENST00000507166.5	TSL:2	c.2403-38C>T		intron	N/A	ENSP00000423325.1
	PDGFRA	ENST00000870889.1		c.3123-38C>T		intron	N/A	ENSP00000540948.1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113258 AN: 151928 Hom.: 44277 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.790

GnomAD2 exomes AF: 0.804 AC: 201190 AN: 250382 AF XY: 0.814

Gnomad AFR exome AF: 0.477

Gnomad AMR exome AF: 0.673

Gnomad ASJ exome AF: 0.921

Gnomad EAS exome AF: 0.859

Gnomad FIN exome AF: 0.874

Gnomad NFE exome AF: 0.861

Gnomad OTH exome AF: 0.840

GnomAD4 exome AF: 0.841 AC: 1217052 AN: 1446414 Hom.: 515955 Cov.: 28 AF XY: 0.843 AC XY: 607375 AN XY: 720650

African (AFR) AF: 0.473 AC: 15721 AN: 33206

American (AMR) AF: 0.682 AC: 30487 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 23858 AN: 26040

East Asian (EAS) AF: 0.858 AC: 33991 AN: 39626

South Asian (SAS) AF: 0.785 AC: 67487 AN: 85964

European-Finnish (FIN) AF: 0.875 AC: 46598 AN: 53236

Middle Eastern (MID) AF: 0.883 AC: 5058 AN: 5730

European-Non Finnish (NFE) AF: 0.860 AC: 943849 AN: 1098040

Other (OTH) AF: 0.835 AC: 50003 AN: 59876

GnomAD4 genome AF: 0.745 AC: 113297 AN: 152046 Hom.: 44288 Cov.: 32 AF XY: 0.747 AC XY: 55496 AN XY: 74318

African (AFR) AF: 0.488 AC: 20228 AN: 41436

American (AMR) AF: 0.739 AC: 11294 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3219 AN: 3472

East Asian (EAS) AF: 0.857 AC: 4408 AN: 5144

South Asian (SAS) AF: 0.761 AC: 3663 AN: 4814

European-Finnish (FIN) AF: 0.870 AC: 9214 AN: 10592

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.861 AC: 58542 AN: 67990

Other (OTH) AF: 0.791 AC: 1668 AN: 2110

Alfa AF: 0.823 Hom.: 202275

Bravo AF: 0.724

Asia WGS AF: 0.759 AC: 2639 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.49
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3733540; hg19: chr4-55161254;