Genetic Variant CSF2RB:c.1013-56A>G (chr22-36932709-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.1013-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,589,592 control chromosomes in the GnomAD database, including 182,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15846 hom., cov: 31)

Exomes 𝑓: 0.47 ( 167145 hom. )

Consequence

CSF2RB
NM_000395.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0590

Publications

8 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 (BayesDel_noAF=-0.85).

BP6

Variant 22-36932709-A-G is Benign according to our data. Variant chr22-36932709-A-G is described in ClinVar as Benign. ClinVar VariationId is 1275163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.1013-56A>G		intron_variant	Intron 8 of 13	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8 link	c.1013-56A>G		intron_variant	Intron 8 of 13	5	NM_000395.3	ENSP00000384053.3
CSF2RB	ENST00000406230.5 link	c.1031-56A>G		intron_variant	Intron 7 of 12	1		ENSP00000385271.1

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65562

AN:

151808

Hom.:

15817

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.535

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.796

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.470

Gnomad OTH

AF:

0.431

GnomAD4 exome

AF:

0.474

AC:

681840

AN:

1437666

Hom.:

167145

AF XY:

0.473

AC XY:

337301

AN XY:

713562

show subpopulations

African (AFR)

AF:

0.228

AC:

7589

AN:

33264

American (AMR)

AF:

0.664

AC:

27778

AN:

41856

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

12480

AN:

25610

East Asian (EAS)

AF:

0.834

AC:

32791

AN:

39310

South Asian (SAS)

AF:

0.437

AC:

36464

AN:

83472

European-Finnish (FIN)

AF:

0.588

AC:

28746

AN:

48924

Middle Eastern (MID)

AF:

0.388

AC:

1909

AN:

4914

European-Non Finnish (NFE)

AF:

0.460

AC:

506187

AN:

1100730

Other (OTH)

AF:

0.468

AC:

27896

AN:

59586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

19254

38508

57761

77015

96269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15196

30392

45588

60784

75980

<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:

0.432

AC:

65636

AN:

151926

Hom.:

15846

Cov.:

AF XY:

0.443

AC XY:

32862

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.237

AC:

9838

AN:

41470

American (AMR)

AF:

0.536

AC:

8186

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

1703

AN:

3468

East Asian (EAS)

AF:

0.797

AC:

4107

AN:

5154

South Asian (SAS)

AF:

0.464

AC:

2231

AN:

4804

European-Finnish (FIN)

AF:

0.604

AC:

6361

AN:

10528

Middle Eastern (MID)

AF:

0.346

AC:

101

AN:

292

European-Non Finnish (NFE)

AF:

0.470

AC:

31885

AN:

67910

Other (OTH)

AF:

0.438

AC:

923

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1768

3536

5305

7073

8841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.439

Hom.:

33336

Bravo

AF:

0.424

Asia WGS

AF:

0.605

AC:

2099

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

-0.85

CADD

Benign

1.2

(source)

DANN

Benign

0.72

PhyloP100

0.059

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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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