rs55830582

Variant names:

• chr4-54274918-G-A
• rs55830582
• NM_006206.6:c.1731G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-54274918-G-A
• chr4-54274918-G-C
• chr4-54274918-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000507166.5(ENSG00000282278):​c.1018-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,614,090 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (48 hom.)
• Consequence: ENSG00000282278 ENST00000507166.5 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:7
• Conservation: PhyloP100: -2.17

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]

ENSG00000282278 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-54274918-G-A is Benign according to our data. Variant chr4-54274918-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 240315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00181 (275/152290) while in subpopulation SAS AF= 0.0232 (112/4830). AF 95% confidence interval is 0.0197. There are 3 homozygotes in gnomad4. There are 162 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.1731G>A	p.Pro577Pro	synonymous_variant	Exon 12 of 23	ENST00000257290.10	NP_006197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.1731G>A	p.Pro577Pro	synonymous_variant	Exon 12 of 23	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1018-7G>A		splice_region_variant, intron_variant	Intron 12 of 23	2		ENSP00000423325.1
PDGFRA	ENST00000509092.5	n.1549G>A		non_coding_transcript_exon_variant	Exon 11 of 15	1
PDGFRA	ENST00000509490.5	n.1731G>A		non_coding_transcript_exon_variant	Exon 12 of 18	1		ENSP00000424218.1

Frequencies

GnomAD3 genomes AF: 0.00179 AC: 273 AN: 152172 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0225

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00348 AC: 874 AN: 251200 Hom.: 14 AF XY: 0.00444 AC XY: 603 AN XY: 135738

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0188

Gnomad FIN exome AF: 0.00222

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.00457

GnomAD4 exome AF: 0.00220 AC: 3210 AN: 1461800 Hom.: 48 Cov.: 33 AF XY: 0.00279 AC XY: 2032 AN XY: 727210

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.000805

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0199

Gnomad4 FIN exome AF: 0.00251

Gnomad4 NFE exome AF: 0.000931

Gnomad4 OTH exome AF: 0.00283

GnomAD4 genome AF: 0.00181 AC: 275 AN: 152290 Hom.: 3 Cov.: 33 AF XY: 0.00218 AC XY: 162 AN XY: 74470

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00169 Hom.: 1

Bravo AF: 0.00117

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.00234

EpiControl AF: 0.00338

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1 Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1 Benign:2

-

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

Variant was observed in a homozygous state in population databases more than expected for disease. Allele frequency is greater than expected for the disorder. A synonymous variant not located in a splice region. -

Sep 22, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Gastrointestinal stromal tumor Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified Benign:1

Jul 22, 2022

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Idiopathic hypereosinophilic syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hereditary cancer-predisposing syndrome Benign:1

Nov 30, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.67

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: rs55830582; hg19: chr4-55141085; COSMIC: COSV104566536; COSMIC: COSV104566536;