X-1282753-C-T

Variant names:

• chrX-1282753-C-T
• NM_172245.4:c.50C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_Moderate BS2_Supporting

The NM_172245.4(CSF2RA):​c.50C>T​(p.Ala17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom. 2 hem.)
• Consequence: CSF2RA NM_172245.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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 Likely_benign. Variant got -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11354947).
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RA	NM_172245.4	c.50C>T	p.Ala17Val	missense_variant	Exon 3 of 13	ENST00000381529.9	NP_758448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RA	ENST00000381529.9	c.50C>T	p.Ala17Val	missense_variant	Exon 3 of 13	1	NM_172245.4	ENSP00000370940.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461546 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727082

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.57
DEOGEN2	Benign	0.14	T;.;T;T;T;.;T;.;.;.
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.60	.;T;.;T;T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Benign	0.26	N;N;N;.;N;N;.;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.50	N;N;N;N;N;N;.;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.43	T;T;T;T;T;T;.;T;T;T
Sift4G	Benign	0.90	T;T;T;T;T;T;D;T;T;T
Polyphen		0.98	D;.;D;.;D;D;.;B;B;B
Vest4		0.11
MutPred		0.33		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.78
MPC		0.14
ClinPred		0.11	T
GERP RS		0.19
Varity_R		0.034

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-1401646;