Genetic Variant CSF2RB:c.-172-108A>G (chr22-36921928-A-G) – ACMG Classification: Benign (-20 pts)

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.-172-108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 560,526 control chromosomes in the GnomAD database, including 72,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16659 hom., cov: 33)

Exomes 𝑓: 0.51 ( 55538 hom. )

Consequence

CSF2RB
NM_000395.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0840

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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 22-36921928-A-G is Benign according to our data. Variant chr22-36921928-A-G is described in ClinVar as [Benign]. Clinvar id is 1266043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.-172-108A>G		intron_variant	Intron 1 of 13	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.-172-108A>G		intron_variant	Intron 1 of 13	5	NM_000395.3	ENSP00000384053.3		P32927-1

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66774

AN:

152002

Hom.:

16650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.576

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.564

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.446

GnomAD4 exome

AF:

0.513

AC:

209658

AN:

408406

Hom.:

55538

AF XY:

0.508

AC XY:

108455

AN XY:

213418

show subpopulations

African (AFR)

AF:

0.191

AC:

2250

AN:

11800

American (AMR)

AF:

0.621

AC:

10952

AN:

17628

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

6471

AN:

12692

East Asian (EAS)

AF:

0.611

AC:

17698

AN:

28944

South Asian (SAS)

AF:

0.406

AC:

17037

AN:

41944

European-Finnish (FIN)

AF:

0.573

AC:

15462

AN:

26990

Middle Eastern (MID)

AF:

0.486

AC:

878

AN:

1808

European-Non Finnish (NFE)

AF:

0.523

AC:

126754

AN:

242562

Other (OTH)

AF:

0.506

AC:

12156

AN:

24038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4615

9229

13844

18458

23073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.439

AC:

66808

AN:

152120

Hom.:

16659

Cov.:

AF XY:

0.446

AC XY:

33135

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.196

AC:

8152

AN:

41502

American (AMR)

AF:

0.578

AC:

8839

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1772

AN:

3472

East Asian (EAS)

AF:

0.576

AC:

2972

AN:

5162

South Asian (SAS)

AF:

0.396

AC:

1911

AN:

4828

European-Finnish (FIN)

AF:

0.564

AC:

5971

AN:

10594

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.524

AC:

35619

AN:

67954

Other (OTH)

AF:

0.449

AC:

948

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1828

3656

5483

7311

9139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.495

Hom.:

7703

Bravo

AF:

0.430

Asia WGS

AF:

0.496

AC:

1722

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.5

(source)

DANN

Benign

0.50

PhyloP100

-0.084

PromoterAI

-0.062

Neutral

(source)

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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22-36921928-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