X-1303972-C-A

Variant names:

• chrX-1303972-C-A
• NM_172245.4:c.996C>A
• CSF2RA p.Ile332Ile

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_172245.4(CSF2RA):​c.996C>A​(p.Ile332Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. I332I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CSF2RA NM_172245.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• 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: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.182 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172245.4. 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
	CSF2RA	NM_172245.4	MANE Select	c.996C>A	p.Ile332Ile	synonymous	Exon 11 of 13	NP_758448.1	P15509-1
	CSF2RA	NM_001161530.2		c.1098C>A	p.Ile366Ile	synonymous	Exon 12 of 14	NP_001155002.1	P15509-7
	CSF2RA	NM_001379153.1		c.1098C>A	p.Ile366Ile	synonymous	Exon 11 of 13	NP_001366082.1	P15509-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.996C>A	p.Ile332Ile	synonymous	Exon 11 of 13	ENSP00000370940.3	P15509-1
	CSF2RA	ENST00000381509.8	TSL:1	c.996C>A	p.Ile332Ile	synonymous	Exon 11 of 13	ENSP00000370920.3	P15509-2
	CSF2RA	ENST00000381524.8	TSL:1	c.996C>A	p.Ile332Ile	synonymous	Exon 11 of 13	ENSP00000370935.3	P15509-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.32
DANN	Benign	0.64
PhyloP100		-0.18

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-1422865;