rs3690

Variant names:

• chr4-54295646-A-C
• rs3690
• NM_006206.6:c.*374A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-54295646-A-C
• chr4-54295646-A-T
• chr4-54295646-A-G

Variant summary

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

The NM_006206.6(PDGFRA):​c.*374A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 371,152 control chromosomes in the GnomAD database, including 6,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3651 hom., cov: 32)
  • Exomes 𝑓: 0.15 (2793 hom.)
• Consequence: PDGFRA NM_006206.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.14
• Publications: 17 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: G2P, Ambry Genetics, Genomics England PanelApp
• congenital heart disease

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

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 4-54295646-A-C is Benign according to our data. Variant chr4-54295646-A-C is described in ClinVar as Benign. ClinVar VariationId is 348916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006206.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	NM_006206.6	MANE Select	c.*374A>C		3_prime_UTR	Exon 23 of 23	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.*374A>C		3_prime_UTR	Exon 24 of 24	NP_001334757.1
	PDGFRA	NM_001347830.2		c.*374A>C		3_prime_UTR	Exon 23 of 23	NP_001334759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.*374A>C		3_prime_UTR	Exon 23 of 23	ENSP00000257290.5	P16234-1
	PDGFRA	ENST00000870889.1		c.*374A>C		3_prime_UTR	Exon 23 of 23	ENSP00000540948.1
	PDGFRA	ENST00000870890.1		c.*374A>C		3_prime_UTR	Exon 23 of 23	ENSP00000540949.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30383 AN: 151996 Hom.: 3653 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.149 AC: 32563 AN: 219038 Hom.: 2793 Cov.: 0 AF XY: 0.151 AC XY: 16553 AN XY: 109618

African (AFR) AF: 0.315 AC: 2615 AN: 8310

American (AMR) AF: 0.262 AC: 2163 AN: 8248

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 686 AN: 8720

East Asian (EAS) AF: 0.140 AC: 2489 AN: 17838

South Asian (SAS) AF: 0.197 AC: 4271 AN: 21666

European-Finnish (FIN) AF: 0.117 AC: 847 AN: 7218

Middle Eastern (MID) AF: 0.0988 AC: 101 AN: 1022

European-Non Finnish (NFE) AF: 0.132 AC: 17370 AN: 131972

Other (OTH) AF: 0.144 AC: 2021 AN: 14044

GnomAD4 genome AF: 0.200 AC: 30394 AN: 152114 Hom.: 3651 Cov.: 32 AF XY: 0.200 AC XY: 14900 AN XY: 74388

African (AFR) AF: 0.322 AC: 13362 AN: 41448

American (AMR) AF: 0.240 AC: 3672 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 236 AN: 3470

East Asian (EAS) AF: 0.143 AC: 741 AN: 5182

South Asian (SAS) AF: 0.238 AC: 1147 AN: 4812

European-Finnish (FIN) AF: 0.130 AC: 1380 AN: 10594

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9366 AN: 68004

Other (OTH) AF: 0.166 AC: 351 AN: 2116

Alfa AF: 0.147 Hom.: 1701

Bravo AF: 0.213

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Gastrointestinal stromal tumor (1)
-	-	1	Idiopathic hypereosinophilic syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		2.1
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: rs3690; hg19: chr4-55161813;