rs1801116

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000395.3(CSF2RB):c.2400G>A(p.Pro800Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,614,078 control chromosomes in the GnomAD database, including 710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 44 hom., cov: 32)

Exomes 𝑓: 0.028 ( 666 hom. )

Consequence

CSF2RB
NM_000395.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.287

Publications

6 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=-0.8).

BP6

Variant 22-36938208-G-A is Benign according to our data. Variant chr22-36938208-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.287 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0231 (3514/152224) while in subpopulation NFE AF = 0.0282 (1917/67990). AF 95% confidence interval is 0.0271. There are 44 homozygotes in GnomAd4. There are 1683 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.2400G>A	p.Pro800Pro	synonymous_variant	Exon 14 of 14	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8 link	c.2400G>A	p.Pro800Pro	synonymous_variant	Exon 14 of 14	5	NM_000395.3	ENSP00000384053.3
CSF2RB	ENST00000406230.5 link	c.2418G>A	p.Pro806Pro	synonymous_variant	Exon 13 of 13	1		ENSP00000385271.1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3512

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0282

Gnomad OTH

AF:

0.0263

GnomAD2 exomes

AF:

0.0229

AC:

5758

AN:

251372

AF XY:

0.0236

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.0309

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0272

Gnomad NFE exome

AF:

0.0294

Gnomad OTH exome

AF:

0.0299

GnomAD4 exome

AF:

0.0284

AC:

41549

AN:

1461854

Hom.:

666

Cov.:

AF XY:

0.0284

AC XY:

20685

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.0162

AC:

544

AN:

33480

American (AMR)

AF:

0.0111

AC:

498

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0332

AC:

869

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0230

AC:

1981

AN:

86258

European-Finnish (FIN)

AF:

0.0280

AC:

1494

AN:

53402

Middle Eastern (MID)

AF:

0.0499

AC:

288

AN:

5766

European-Non Finnish (NFE)

AF:

0.0308

AC:

34305

AN:

1111996

Other (OTH)

AF:

0.0260

AC:

1569

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2769

5538

8306

11075

13844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1316

2632

3948

5264

6580

<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:

0.0231

AC:

3514

AN:

152224

Hom.:

Cov.:

AF XY:

0.0226

AC XY:

1683

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0164

AC:

681

AN:

41538

American (AMR)

AF:

0.0202

AC:

309

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

117

AN:

3470

East Asian (EAS)

AF:

0.000388

AC:

AN:

5160

South Asian (SAS)

AF:

0.0232

AC:

112

AN:

4822

European-Finnish (FIN)

AF:

0.0245

AC:

260

AN:

10622

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0282

AC:

1917

AN:

67990

Other (OTH)

AF:

0.0260

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

170

340

510

680

850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0275

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0293

EpiControl

AF:

0.0291

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Pro800Pro 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 2.8% (245/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1801116). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.5

(source)

DANN

Benign

0.40

PhyloP100

0.29

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over