rs117805308

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.934G>A(p.Asp312Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,613,890 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D312G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.013 ( 14 hom., cov: 32)

Exomes 𝑓: 0.017 ( 260 hom. )

Consequence

CSF2RB
NM_000395.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.388

Publications

16 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=0.004304707).

BP6

Variant 22-36930752-G-A is Benign according to our data. Variant chr22-36930752-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226556.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 = 0.0127 (1927/152222) while in subpopulation NFE AF = 0.0211 (1436/68020). AF 95% confidence interval is 0.0202. There are 14 homozygotes in GnomAd4. There are 904 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.934G>A	p.Asp312Asn	missense_variant	Exon 8 of 14	ENST00000403662.8	NP_000386.1	P32927-1Q6NSJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSF2RB	ENST00000403662.8 link	c.934G>A	p.Asp312Asn	missense_variant	Exon 8 of 14	5	NM_000395.3	ENSP00000384053.3	P32927-1
CSF2RB	ENST00000406230.5 link	c.952G>A	p.Asp318Asn	missense_variant	Exon 7 of 13	1		ENSP00000385271.1	P32927-2
CSF2RB	ENST00000421539.1 link	c.*8G>A		downstream_gene_variant		5		ENSP00000393585.1	B0QY07

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1929

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.0123

AC:

3093

AN:

251242

AF XY:

0.0126

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.00923

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0143

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0171

AC:

25053

AN:

1461668

Hom.:

260

Cov.:

AF XY:

0.0167

AC XY:

12159

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.00290

AC:

AN:

33474

American (AMR)

AF:

0.00541

AC:

242

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

279

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00424

AC:

366

AN:

86250

European-Finnish (FIN)

AF:

0.0143

AC:

760

AN:

53314

Middle Eastern (MID)

AF:

0.00353

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.0200

AC:

22295

AN:

1112010

Other (OTH)

AF:

0.0165

AC:

994

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1657

3314

4972

6629

8286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.0127

AC:

1927

AN:

152222

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

904

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.00383

AC:

159

AN:

41526

American (AMR)

AF:

0.00621

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00270

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0123

AC:

131

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0211

AC:

1436

AN:

68020

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

102

204

306

408

510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0182

Hom.:

Bravo

AF:

0.0116

TwinsUK

AF:

0.0221

AC:

ALSPAC

AF:

0.0205

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0205

AC:

176

ExAC

AF:

0.0132

AC:

1597

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0178

EpiControl

AF:

0.0145

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

- -

Jul 12, 2022

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Breakthrough Genomics, Breakthrough Genomics

Significance: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

Asp312Asn in exon 8 of CSF2RB: This variant is not expected to have clinical sig nificance because it has been identified in 2.0% (176/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs117805308). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.68

D;T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.70

T;T;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.74

N;.;.

PhyloP100

0.39

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.5

N;.;N

REVEL

Benign

0.12

Sift

Benign

0.51

T;.;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.51

P;.;B

Vest4

0.24

MPC

0.15

ClinPred

0.00057

GERP RS

2.1

Varity_R

0.039

gMVP

0.37

Mutation Taster

=98/2

polymorphism

(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