X-1282541-A-G

Variant summary

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

The ENST00000432318.8(CSF2RA):c.-46A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 747,374 control chromosomes in the GnomAD database, including 4,617 homozygotes. There are 39,899 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (752 hom., 6459 hem., cov: 31)
  • Exomes 𝑓: 0.11 (3865 hom. 33440 hem.)
• Consequence: CSF2RA ENST00000432318.8 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0180

Genes affected

CSF2RA (HGNC:2435): (colony stimulating factor 2 receptor subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric receptor for colony stimulating factor 2, a cytokine which controls the production, differentiation, and function of granulocytes and macrophages. The encoded protein is a member of the cytokine family of receptors. This gene is found in the pseudoautosomal region (PAR) of the X and Y chromosomes. Multiple transcript variants encoding different isoforms have been found for this gene, with some of the isoforms being membrane-bound and others being soluble. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-1282541-A-G is Benign according to our data. Variant chrX-1282541-A-G is described in ClinVar as [Benign]. Clinvar id is 1265683.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RA	NM_172245.4	c.-26-137A>G		intron_variant		ENST00000381529.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RA	ENST00000381529.9	c.-26-137A>G		intron_variant		1	NM_172245.4	A2

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12908 AN: 151894 Hom.: 753 Cov.: 31 AF XY: 0.0871 AC XY: 6458 AN XY: 74142

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.0529

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.0738

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.107 AC: 63434 AN: 595362 Hom.: 3865 Cov.: 5 AF XY: 0.104 AC XY: 33440 AN XY: 321414

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.0714

Gnomad4 EAS exome AF: 0.0409

Gnomad4 SAS exome AF: 0.0792

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.0949

GnomAD4 genome AF: 0.0849 AC: 12903 AN: 152012 Hom.: 752 Cov.: 31 AF XY: 0.0870 AC XY: 6459 AN XY: 74270

Gnomad4 AFR AF: 0.0223

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0720

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0715

Bravo AF: 0.0812

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

Mar 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.1
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs28733318; hg19: chrX-1401434;