chr22-36922235-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000395.3(CSF2RB):c.28A>G(p.Met10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,590,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CSF2RB
NM_000395.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.632

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 links:

ENSG00000304449 (HGNC:):

ENSG00000304449 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.072481394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.28A>G	p.Met10Val	missense_variant	Exon 2 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.28A>G	p.Met10Val	missense_variant	Exon 2 of 14	5	NM_000395.3	ENSP00000384053.3		P32927-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000470

AC:

AN:

212540

AF XY:

0.0000436

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000189

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1438682

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

713394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33146

American (AMR)

AF:

0.000239

AC:

AN:

41924

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25602

East Asian (EAS)

AF:

0.00

AC:

AN:

38754

South Asian (SAS)

AF:

0.0000243

AC:

AN:

82418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4506

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1101530

Other (OTH)

AF:

0.0000168

AC:

AN:

59378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.000196

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

May 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 10 of the CSF2RB protein (p.Met10Val). This variant is present in population databases (rs754457287, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CSF2RB-related conditions. ClinVar contains an entry for this variant (Variation ID: 1495547). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.0090

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.25

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

-0.090

N;.;N

PhyloP100

-0.63

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.37

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.42

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.072

MutPred

0.59

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.55

MPC

0.15

ClinPred

0.029

GERP RS

-7.5

PromoterAI

0.010

Neutral

(source)

Varity_R

0.031

gMVP

0.35

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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chr22-36922235-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over