NM_000395.3:c.1807C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000395.3(CSF2RB):c.1807C>A(p.Pro603Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,572,632 control chromosomes in the GnomAD database, including 1,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 101 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1239 hom. )

Consequence

CSF2RB
NM_000395.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.00

Publications

15 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054210126).

BP6

Variant 22-36937615-C-A is Benign according to our data. Variant chr22-36937615-C-A is described in ClinVar as Benign. ClinVar VariationId is 504754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0301 (4587/152284) while in subpopulation NFE AF = 0.0446 (3034/68000). AF 95% confidence interval is 0.0433. There are 101 homozygotes in GnomAd4. There are 2260 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 101 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.1807C>A	p.Pro603Thr	missense_variant	Exon 14 of 14	ENST00000403662.8	NP_000386.1	P32927-1Q6NSJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8 link	c.1807C>A	p.Pro603Thr	missense_variant	Exon 14 of 14	5	NM_000395.3	ENSP00000384053.3		P32927-1
CSF2RB	ENST00000406230.5 link	c.1825C>A	p.Pro609Thr	missense_variant	Exon 13 of 13	1		ENSP00000385271.1		P32927-2

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

4586

AN:

152166

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00692

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0280

Gnomad FIN

AF:

0.0529

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0446

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0318

AC:

5679

AN:

178744

AF XY:

0.0334

show subpopulations

Gnomad AFR exome

AF:

0.00559

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.0227

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0529

Gnomad NFE exome

AF:

0.0445

Gnomad OTH exome

AF:

0.0322

GnomAD4 exome

AF:

0.0399

AC:

56717

AN:

1420348

Hom.:

1239

Cov.:

AF XY:

0.0399

AC XY:

28009

AN XY:

702762

show subpopulations

African (AFR)

AF:

0.00563

AC:

183

AN:

32478

American (AMR)

AF:

0.0140

AC:

529

AN:

37902

Ashkenazi Jewish (ASJ)

AF:

0.0238

AC:

603

AN:

25322

East Asian (EAS)

AF:

0.0000536

AC:

AN:

37280

South Asian (SAS)

AF:

0.0284

AC:

2335

AN:

82310

European-Finnish (FIN)

AF:

0.0566

AC:

2822

AN:

49878

Middle Eastern (MID)

AF:

0.0392

AC:

224

AN:

5712

European-Non Finnish (NFE)

AF:

0.0440

AC:

47977

AN:

1090662

Other (OTH)

AF:

0.0347

AC:

2042

AN:

58804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

3564

7129

10693

14258

17822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1794

3588

5382

7176

8970

<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:

0.0301

AC:

4587

AN:

152284

Hom.:

101

Cov.:

AF XY:

0.0304

AC XY:

2260

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00690

AC:

287

AN:

41568

American (AMR)

AF:

0.0236

AC:

361

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.0284

AC:

137

AN:

4826

European-Finnish (FIN)

AF:

0.0529

AC:

562

AN:

10620

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0446

AC:

3034

AN:

68000

Other (OTH)

AF:

0.0255

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

225

450

674

899

1124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0390

Hom.:

380

Bravo

AF:

0.0265

TwinsUK

AF:

0.0405

AC:

150

ALSPAC

AF:

0.0433

AC:

167

ESP6500AA

AF:

0.00516

AC:

ESP6500EA

AF:

0.0364

AC:

305

ExAC

AF:

0.0255

AC:

3001

Asia WGS

AF:

0.00808

AC:

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

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 21205713, 20981092, 9410898, 27884173) -

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 26, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Pro603Thr in exon 14 of CSF2RB: This variant is not expected to have clinical significance because it has been identified in 3.6% (305/8368) of European Ameri can chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington. edu/EVS/; dbSNP rs1801122). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

D;T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.78

T;T;T

MetaRNN

Benign

0.0054

T;T;T

MetaSVM

Uncertain

0.42

MutationAssessor

Benign

1.9

L;.;.

PhyloP100

1.0

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.064

MPC

0.50

ClinPred

0.011

GERP RS

5.4

Varity_R

0.19

gMVP

0.34

Mutation Taster

=98/2

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