rs1801117

Positions:

• chr22-36933957-C-G
• chr22-36933957-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000395.3(CSF2RB):​c.1278C>G​(p.Ser426Arg) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S426S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CSF2RB NM_000395.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.1278C>G	p.Ser426Arg	missense_variant	10/14	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.1278C>G	p.Ser426Arg	missense_variant	10/14	5	NM_000395.3	ENSP00000384053	P1
CSF2RB	ENST00000406230.5	c.1296C>G	p.Ser432Arg	missense_variant	9/13	1		ENSP00000385271

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151888 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 38

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151888 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74174

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D;T;.
Eigen	Benign	-0.084
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.81	T;T;T
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.8	M;.;.
MutationTaster	Benign	0.95	D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.3	D;.;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0060	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.86
MutPred		0.54		Gain of MoRF binding (P = 0.0253);Gain of MoRF binding (P = 0.0253);.;
MVP		0.91
MPC		0.69
ClinPred		0.99	D
GERP RS		0.24
Varity_R		0.78
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.37		Position offset: 37

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

Publications

LitVar

Other links and lift over

dbSNP: rs1801117; hg19: chr22-37329999;