rs771435926

Variant names:

• chrX-1282717-T-C
• rs771435926
• NM_172245.4:c.14T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_172245.4(CSF2RA):​c.14T>C​(p.Val5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,424 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V5V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: CSF2RA NM_172245.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.81
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047418207).

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.14T>C	p.Val5Ala	missense	Exon 3 of 13	NP_758448.1	P15509-1
	CSF2RA	NM_001161530.2		c.14T>C	p.Val5Ala	missense	Exon 3 of 14	NP_001155002.1	P15509-7
	CSF2RA	NM_001379153.1		c.14T>C	p.Val5Ala	missense	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.14T>C	p.Val5Ala	missense	Exon 3 of 13	ENSP00000370940.3	P15509-1
	CSF2RA	ENST00000381509.8	TSL:1	c.14T>C	p.Val5Ala	missense	Exon 3 of 13	ENSP00000370920.3	P15509-2
	CSF2RA	ENST00000381524.8	TSL:1	c.14T>C	p.Val5Ala	missense	Exon 3 of 13	ENSP00000370935.3	P15509-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251180 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461424 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727028

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

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

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111622

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

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_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.033
DANN	Benign	0.27
DEOGEN2	Benign	0.14	T
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-1.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.10
Sift	Benign	0.77	T
Sift4G	Benign	1.0	T
Polyphen		0.017	B
Vest4		0.057
MutPred		0.37		Loss of sheet (P = 0.0054)
MVP		0.55
MPC		0.14
ClinPred		0.013	T
GERP RS		-0.36
PromoterAI		0.041	Neutral
Varity_R		0.026
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs771435926; hg19: chrX-1401610;