22-36937752-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000395.3(CSF2RB):c.1944A>G(p.Pro648Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,569,224 control chromosomes in the GnomAD database, including 522,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 46289 hom., cov: 31)

Exomes 𝑓: 0.82 ( 476086 hom. )

Consequence

CSF2RB
NM_000395.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.270

Publications

24 publications found

Variant links:

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]

CSF2RB Gene-Disease associations (from GenCC):

surfactant metabolism dysfunction, pulmonary, 5
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
hereditary pulmonary alveolar proteinosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CSF2RB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 22-36937752-A-G is Benign according to our data. Variant chr22-36937752-A-G is described in ClinVar as Benign. ClinVar VariationId is 226549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000395.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	NM_000395.3	MANE Select	c.1944A>G	p.Pro648Pro	synonymous	Exon 14 of 14	NP_000386.1
	CSF2RB	NM_001410827.1		c.1962A>G	p.Pro654Pro	synonymous	Exon 14 of 14	NP_001397756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.1944A>G	p.Pro648Pro	synonymous	Exon 14 of 14	ENSP00000384053.3
	CSF2RB	ENST00000406230.5	TSL:1	c.1962A>G	p.Pro654Pro	synonymous	Exon 13 of 13	ENSP00000385271.1

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117655

AN:

151950

Hom.:

46252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.637

Gnomad AMI

AF:

0.751

Gnomad AMR

AF:

0.821

Gnomad ASJ

AF:

0.785

Gnomad EAS

AF:

0.939

Gnomad SAS

AF:

0.876

Gnomad FIN

AF:

0.861

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.814

Gnomad OTH

AF:

0.776

GnomAD2 exomes

AF:

0.833

AC:

149507

AN:

179536

AF XY:

0.834

show subpopulations

Gnomad AFR exome

AF:

0.634

Gnomad AMR exome

AF:

0.886

Gnomad ASJ exome

AF:

0.784

Gnomad EAS exome

AF:

0.944

Gnomad FIN exome

AF:

0.867

Gnomad NFE exome

AF:

0.809

Gnomad OTH exome

AF:

0.817

GnomAD4 exome

AF:

0.818

AC:

1159801

AN:

1417156

Hom.:

476086

Cov.:

AF XY:

0.819

AC XY:

574293

AN XY:

700912

show subpopulations

African (AFR)

AF:

0.625

AC:

20345

AN:

32566

American (AMR)

AF:

0.879

AC:

32521

AN:

36990

Ashkenazi Jewish (ASJ)

AF:

0.789

AC:

19979

AN:

25316

East Asian (EAS)

AF:

0.945

AC:

35399

AN:

37456

South Asian (SAS)

AF:

0.865

AC:

70570

AN:

81570

European-Finnish (FIN)

AF:

0.866

AC:

43197

AN:

49898

Middle Eastern (MID)

AF:

0.766

AC:

4362

AN:

5692

European-Non Finnish (NFE)

AF:

0.813

AC:

885586

AN:

1088962

Other (OTH)

AF:

0.815

AC:

47842

AN:

58706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

14259

28518

42777

57036

71295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20638

41276

61914

82552

103190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.774

AC:

117750

AN:

152068

Hom.:

46289

Cov.:

AF XY:

0.779

AC XY:

57930

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.638

AC:

26454

AN:

41486

American (AMR)

AF:

0.822

AC:

12559

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.785

AC:

2724

AN:

3472

East Asian (EAS)

AF:

0.940

AC:

4827

AN:

5136

South Asian (SAS)

AF:

0.876

AC:

4227

AN:

4826

European-Finnish (FIN)

AF:

0.861

AC:

9141

AN:

10614

Middle Eastern (MID)

AF:

0.731

AC:

215

AN:

294

European-Non Finnish (NFE)

AF:

0.814

AC:

55278

AN:

67932

Other (OTH)

AF:

0.777

AC:

1642

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1295

2590

3885

5180

6475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

862

1724

2586

3448

4310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.799

Hom.:

68521

Bravo

AF:

0.767

Asia WGS

AF:

0.866

AC:

3013

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Nov 28, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Pro648Pro in exon 14 of CSF2RB: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 34.1% (1489/4366) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs131840).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.4

(source)

DANN

Benign

0.18

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over