chr4-54229560-A-AT

Variant names:

• chr4-54229560-A-AT
• rs920838716
• NM_006206.6:c.-13+156dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_006206.6(PDGFRA):​c.-13+156dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 315,112 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0087 (12 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1 hom.)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.284

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-54229560-A-AT is Benign according to our data. Variant chr4-54229560-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 1195004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00867 (1290/148744) while in subpopulation AFR AF = 0.0271 (1104/40670). AF 95% confidence interval is 0.0258. There are 12 homozygotes in GnomAd4. There are 583 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1290 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFRA	NM_006206.6	c.-13+156dupT		intron_variant	Intron 1 of 22	ENST00000257290.10	NP_006197.1
PDGFRA	NM_001347828.2	c.-16+156dupT		intron_variant	Intron 1 of 23		NP_001334757.1
PDGFRA	NM_001347827.2	c.-13+156dupT		intron_variant	Intron 1 of 16		NP_001334756.1
PDGFRA	XM_006714041.4	c.-16+156dupT		intron_variant	Intron 1 of 17		XP_006714104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFRA	ENST00000257290.10	c.-13+156dupT		intron_variant	Intron 1 of 22	1	NM_006206.6	ENSP00000257290.5
ENSG00000282278	ENST00000507166.5	c.1018-45354dupT		intron_variant	Intron 12 of 23	2		ENSP00000423325.1

Frequencies

GnomAD3 genomes AF: 0.00869 AC: 1292 AN: 148682 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00293

Gnomad SAS AF: 0.000848

Gnomad FIN AF: 0.00103

Gnomad MID AF: 0.0160

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.00891

GnomAD4 exome AF: 0.0377 AC: 6277 AN: 166368 Hom.: 1 AF XY: 0.0370 AC XY: 3114 AN XY: 84252

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0617 AC: 306 AN: 4960

American (AMR) AF: 0.0418 AC: 213 AN: 5096

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 228 AN: 6048

East Asian (EAS) AF: 0.0350 AC: 553 AN: 15818

South Asian (SAS) AF: 0.0334 AC: 49 AN: 1466

European-Finnish (FIN) AF: 0.0321 AC: 464 AN: 14442

Middle Eastern (MID) AF: 0.0353 AC: 31 AN: 878

European-Non Finnish (NFE) AF: 0.0374 AC: 3986 AN: 106660

Other (OTH) AF: 0.0406 AC: 447 AN: 11000

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00867 AC: 1290 AN: 148744 Hom.: 12 Cov.: 31 AF XY: 0.00804 AC XY: 583 AN XY: 72482

African (AFR) AF: 0.0271 AC: 1104 AN: 40670

American (AMR) AF: 0.00497 AC: 74 AN: 14898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00274 AC: 14 AN: 5112

South Asian (SAS) AF: 0.000851 AC: 4 AN: 4698

European-Finnish (FIN) AF: 0.00103 AC: 10 AN: 9738

Middle Eastern (MID) AF: 0.0175 AC: 5 AN: 286

European-Non Finnish (NFE) AF: 0.000911 AC: 61 AN: 66966

Other (OTH) AF: 0.00882 AC: 18 AN: 2040

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 30, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs920838716; hg19: chr4-55095727;