NM_172245.4:c.15G>T

Variant names:

• chrX-1282718-G-T
• rs372682829
• NM_172245.4:c.15G>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_172245.4(CSF2RA):​c.15G>T​(p.Val5Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000768 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 63 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., 4 hem., cov: 31)
  • Exomes 𝑓: 0.000074 (0 hom. 59 hem.)
• Consequence: CSF2RA NM_172245.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.855
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-1282718-G-T is Benign according to our data. Variant chrX-1282718-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1146418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.855 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000739 (108/1461518) while in subpopulation MID AF = 0.000694 (4/5762). AF 95% confidence interval is 0.000236. There are 0 homozygotes in GnomAdExome4. There are 59 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 4 AR gene

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.15G>T	p.Val5Val	synonymous	Exon 3 of 13	NP_758448.1	P15509-1
	CSF2RA	NM_001161530.2		c.15G>T	p.Val5Val	synonymous	Exon 3 of 14	NP_001155002.1	P15509-7
	CSF2RA	NM_001379153.1		c.15G>T	p.Val5Val	synonymous	Exon 2 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.15G>T	p.Val5Val	synonymous	Exon 3 of 13	ENSP00000370940.3	P15509-1
	CSF2RA	ENST00000381509.8	TSL:1	c.15G>T	p.Val5Val	synonymous	Exon 3 of 13	ENSP00000370920.3	P15509-2
	CSF2RA	ENST00000381524.8	TSL:1	c.15G>T	p.Val5Val	synonymous	Exon 3 of 13	ENSP00000370935.3	P15509-1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152080 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.0000995 AC: 25 AN: 251180 AF XY: 0.0000958

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.000694

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000881

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.0000739 AC: 108 AN: 1461518 Hom.: 0 Cov.: 30 AF XY: 0.0000811 AC XY: 59 AN XY: 727072

African (AFR) AF: 0.0000299 AC: 1 AN: 33464

American (AMR) AF: 0.000201 AC: 9 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1111706

Other (OTH) AF: 0.000331 AC: 20 AN: 60370

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152080 Hom.: 0 Cov.: 31 AF XY: 0.0000539 AC XY: 4 AN XY: 74280

African (AFR) AF: 0.0000483 AC: 2 AN: 41432

American (AMR) AF: 0.000262 AC: 4 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68014

Other (OTH) AF: 0.00144 AC: 3 AN: 2088

Bravo AF: 0.000155

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Surfactant metabolism dysfunction, pulmonary, 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.37
PhyloP100		-0.85
PromoterAI		-0.023	Neutral
Mutation Taster		=299/1	polymorphism

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: rs372682829; hg19: chrX-1401611;