22-36922267-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000395.3(CSF2RB):c.60C>A(p.Ser20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,578,894 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (3 hom.)
• Consequence: CSF2RB NM_000395.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041003227).
• BP6: Variant 22-36922267-C-A is Benign according to our data. Variant chr22-36922267-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1168184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.60C>A	p.Ser20Arg	missense_variant	2/14	ENST00000403662.8
LOC105373023	XR_938230.2	n.195-3328G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.60C>A	p.Ser20Arg	missense_variant	2/14	5	NM_000395.3	P1
CSF2RB	ENST00000406230.5	c.60C>A	p.Ser20Arg	missense_variant	1/13	1

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 55 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00945

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000985 AC: 188 AN: 190856 Hom.: 0 AF XY: 0.000918 AC XY: 94 AN XY: 102398

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000698

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0124

Gnomad SAS exome AF: 0.0000401

Gnomad FIN exome AF: 0.0000597

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.000400

GnomAD4 exome AF: 0.000289 AC: 412 AN: 1426626 Hom.: 3 Cov.: 31 AF XY: 0.000266 AC XY: 188 AN XY: 706382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000501

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00885

Gnomad4 SAS exome AF: 0.0000492

Gnomad4 FIN exome AF: 0.0000197

Gnomad4 NFE exome AF: 0.0000283

Gnomad4 OTH exome AF: 0.000627

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152268 Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28 AN XY: 74454

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00947

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.0000213 Hom.: 0

Bravo AF: 0.000434

ExAC AF: 0.000700 AC: 84

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	CSF2RB: BP4, BS1 -

CSF2RB-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	0.020
Dann	Benign	0.41
DEOGEN2	Benign	0.31	T;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.39	T;T;T
MetaRNN	Benign	0.0041	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.1	L;.;L
MutationTaster	Benign	1.0	N;N;N
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		0.0057	T
GERP RS		-6.8
Varity_R		0.043
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;