X-1294564-C-G

Variant names:

• chrX-1294564-C-G
• rs28414810
• NM_172245.4:c.780+103C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_172245.4(CSF2RA):​c.780+103C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,481,270 control chromosomes in the GnomAD database, including 321,038 homozygotes. There are 485,467 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (34682 hom., 50056 hem., cov: 31)
  • Exomes 𝑓: 0.66 (286356 hom. 435411 hem.)
• Consequence: CSF2RA NM_172245.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0350
• Publications: 0 publications found

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]

CSF2RA Gene-Disease associations (from GenCC):

• surfactant metabolism dysfunction, pulmonary, 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-1294564-C-G is Benign according to our data. Variant chrX-1294564-C-G is described in ClinVar as Benign. ClinVar VariationId is 1263327.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RA	NM_172245.4	c.780+103C>G		intron_variant	Intron 8 of 12	ENST00000381529.9	NP_758448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RA	ENST00000381529.9	c.780+103C>G		intron_variant	Intron 8 of 12	1	NM_172245.4	ENSP00000370940.3

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102321 AN: 151726 Hom.: 34652 Cov.: 31

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.655 AC: 871069 AN: 1329426 Hom.: 286356 AF XY: 0.657 AC XY: 435411 AN XY: 662500

African (AFR) AF: 0.738 AC: 22813 AN: 30894

American (AMR) AF: 0.585 AC: 24067 AN: 41140

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 19328 AN: 24670

East Asian (EAS) AF: 0.616 AC: 23744 AN: 38530

South Asian (SAS) AF: 0.720 AC: 59461 AN: 82564

European-Finnish (FIN) AF: 0.703 AC: 36287 AN: 51606

Middle Eastern (MID) AF: 0.718 AC: 2928 AN: 4078

European-Non Finnish (NFE) AF: 0.645 AC: 645075 AN: 1000158

Other (OTH) AF: 0.670 AC: 37366 AN: 55786

GnomAD4 genome AF: 0.674 AC: 102407 AN: 151844 Hom.: 34682 Cov.: 31 AF XY: 0.675 AC XY: 50056 AN XY: 74158

African (AFR) AF: 0.731 AC: 30296 AN: 41452

American (AMR) AF: 0.630 AC: 9591 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2736 AN: 3468

East Asian (EAS) AF: 0.586 AC: 3020 AN: 5152

South Asian (SAS) AF: 0.723 AC: 3478 AN: 4810

European-Finnish (FIN) AF: 0.689 AC: 7280 AN: 10562

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.645 AC: 43769 AN: 67868

Other (OTH) AF: 0.661 AC: 1393 AN: 2108

Bravo AF: 0.667

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 22, 2018

GeneDx

Significance: 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
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.12
PhyloP100		0.035

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: rs28414810; hg19: chrX-1413457;