rs1801114

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000395.3(CSF2RB):c.1954G>A(p.Val652Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,574,552 control chromosomes in the GnomAD database, including 1,385 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 443 hom., cov: 32)

Exomes 𝑓: 0.026 ( 942 hom. )

Consequence

CSF2RB
NM_000395.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.05

Publications

11 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=0.001535207).

BP6

Variant 22-36937762-G-A is Benign according to our data. Variant chr22-36937762-G-A is described in ClinVar as Benign. ClinVar VariationId is 226550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.1954G>A	p.Val652Met	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.1954G>A	p.Val652Met	missense_variant	Exon 14 of 14	5	NM_000395.3	ENSP00000384053.3		P32927-1
CSF2RB	ENST00000406230.5 link	c.1972G>A	p.Val658Met	missense_variant	Exon 13 of 13	1		ENSP00000385271.1		P32927-2

Frequencies

GnomAD3 genomes

AF:

0.0547

AC:

8314

AN:

152102

Hom.:

439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0349

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0676

Gnomad FIN

AF:

0.00442

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0206

Gnomad OTH

AF:

0.0506

GnomAD2 exomes

AF:

0.0304

AC:

5634

AN:

185336

AF XY:

0.0304

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.0266

Gnomad EAS exome

AF:

0.000288

Gnomad FIN exome

AF:

0.00487

Gnomad NFE exome

AF:

0.0202

Gnomad OTH exome

AF:

0.0294

GnomAD4 exome

AF:

0.0255

AC:

36326

AN:

1422332

Hom.:

942

Cov.:

AF XY:

0.0261

AC XY:

18363

AN XY:

703938

show subpopulations

African (AFR)

AF:

0.152

AC:

4971

AN:

32808

American (AMR)

AF:

0.0240

AC:

898

AN:

37402

Ashkenazi Jewish (ASJ)

AF:

0.0262

AC:

665

AN:

25380

East Asian (EAS)

AF:

0.000211

AC:

AN:

37954

South Asian (SAS)

AF:

0.0556

AC:

4563

AN:

82096

European-Finnish (FIN)

AF:

0.00617

AC:

310

AN:

50218

Middle Eastern (MID)

AF:

0.0577

AC:

330

AN:

5718

European-Non Finnish (NFE)

AF:

0.0208

AC:

22763

AN:

1091850

Other (OTH)

AF:

0.0309

AC:

1818

AN:

58906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

2256

4511

6767

9022

11278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

980

1960

2940

3920

4900

<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:

0.0548

AC:

8337

AN:

152220

Hom.:

443

Cov.:

AF XY:

0.0531

AC XY:

3953

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.139

AC:

5769

AN:

41516

American (AMR)

AF:

0.0348

AC:

533

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0245

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5166

South Asian (SAS)

AF:

0.0676

AC:

326

AN:

4820

European-Finnish (FIN)

AF:

0.00442

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0206

AC:

1402

AN:

67996

Other (OTH)

AF:

0.0501

AC:

106

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

388

777

1165

1554

1942

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0286

Hom.:

240

Bravo

AF:

0.0597

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0239

AC:

ESP6500AA

AF:

0.134

AC:

588

ESP6500EA

AF:

0.0197

AC:

168

ExAC

AF:

0.0290

AC:

3453

Asia WGS

AF:

0.0310

AC:

108

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

Jan 31, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Val652Met in exon 14 of CSF2RB: This variant is not expected to have clinical si gnificance because it has been identified in 13.4% (588/4378) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs1801114). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.30

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.24

T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.34

T;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.0

L;.;.

PhyloP100

-1.1

PrimateAI

Benign

0.30

PROVEAN

Benign

0.13

N;.;N

REVEL

Benign

0.22

Sift

Benign

0.27

T;.;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.019

B;.;B

Vest4

0.039

MPC

0.15

ClinPred

0.0022

GERP RS

-7.8

Varity_R

0.017

gMVP

0.075

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over