22-36922267-C-G

Variant names:

• chr22-36922267-C-G
• rs200588212
• NM_000395.3:c.60C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000395.3(CSF2RB):​c.60C>G​(p.Ser20Arg) variant causes a missense 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. 16/21 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: 33)
• Consequence: CSF2RB NM_000395.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

Genes affected

CSF2RB (HGNC:2436): (colony stimulating factor 2 receptor subunit beta) The protein encoded by this gene is the common beta chain of the high affinity receptor for IL-3, IL-5 and CSF. Defects in this gene have been reported to be associated with protein alveolar proteinosis (PAP). [provided by RefSeq, Jul 2008]

LOC105373023 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07645053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.60C>G	p.Ser20Arg	missense_variant	Exon 2 of 14	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.60C>G	p.Ser20Arg	missense_variant	Exon 2 of 14	5	NM_000395.3	ENSP00000384053.3
CSF2RB	ENST00000406230.5	c.60C>G	p.Ser20Arg	missense_variant	Exon 1 of 13	1		ENSP00000385271.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.024
DANN	Benign	0.33
DEOGEN2	Benign	0.31	T;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.39	T;T;T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.1	L;.;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.11	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.72	T;T;T
Sift4G	Benign	0.60	T;T;T
Polyphen		0.0030	B;.;B
Vest4		0.11
MutPred		0.26		Loss of glycosylation at S20 (P = 0.0586);Loss of glycosylation at S20 (P = 0.0586);Loss of glycosylation at S20 (P = 0.0586);
MVP		0.56
MPC		0.17
ClinPred		0.036	T
GERP RS		-6.8
Varity_R		0.043
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200588212; hg19: chr22-37318309;