dbSNP rs16997510: CSF2RB:c.1569-13T>G (chr22-36937364-T-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.1569-13T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,611,906 control chromosomes in the GnomAD database, including 2,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 577 hom., cov: 31)

Exomes 𝑓: 0.032 ( 1506 hom. )

Consequence

CSF2RB
NM_000395.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.86

Publications

5 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: DEFINITIVE, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
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=-0.89).

BP6

Variant 22-36937364-T-G is Benign according to our data. Variant chr22-36937364-T-G is described in ClinVar as Benign. ClinVar VariationId is 226547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000395.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	NM_000395.3	MANE Select	c.1569-13T>G		intron	N/A	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.1587-13T>G		intron	N/A	NP_001397756.1	P32927-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.1569-13T>G	intron	N/A	ENSP00000384053.3	P32927-1
CSF2RB	ENST00000406230.5	TSL:1	c.1587-13T>G	intron	N/A	ENSP00000385271.1	P32927-2
CSF2RB	ENST00000910856.1		c.1605-13T>G	intron	N/A	ENSP00000580915.1

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9590

AN:

151432

Hom.:

569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.0560

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.00526

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0239

Gnomad OTH

AF:

0.0602

GnomAD2 exomes

AF:

0.0418

AC:

10385

AN:

248670

AF XY:

0.0429

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.0326

Gnomad EAS exome

AF:

0.00723

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.0250

Gnomad OTH exome

AF:

0.0397

GnomAD4 exome

AF:

0.0323

AC:

47223

AN:

1460356

Hom.:

1506

Cov.:

AF XY:

0.0341

AC XY:

24762

AN XY:

726568

show subpopulations

African (AFR)

AF:

0.167

AC:

5595

AN:

33472

American (AMR)

AF:

0.0267

AC:

1192

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0316

AC:

825

AN:

26134

East Asian (EAS)

AF:

0.00786

AC:

312

AN:

39700

South Asian (SAS)

AF:

0.102

AC:

8775

AN:

86244

European-Finnish (FIN)

AF:

0.0119

AC:

619

AN:

52058

Middle Eastern (MID)

AF:

0.0711

AC:

408

AN:

5738

European-Non Finnish (NFE)

AF:

0.0244

AC:

27128

AN:

1111918

Other (OTH)

AF:

0.0392

AC:

2369

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

2426

4852

7277

9703

12129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1162

2324

3486

4648

5810

<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:

0.0635

AC:

9622

AN:

151550

Hom.:

577

Cov.:

AF XY:

0.0624

AC XY:

4618

AN XY:

74044

show subpopulations

African (AFR)

AF:

0.156

AC:

6436

AN:

41228

American (AMR)

AF:

0.0368

AC:

561

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

103

AN:

3470

East Asian (EAS)

AF:

0.00527

AC:

AN:

5124

South Asian (SAS)

AF:

0.120

AC:

571

AN:

4776

European-Finnish (FIN)

AF:

0.0104

AC:

109

AN:

10526

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0239

AC:

1621

AN:

67900

Other (OTH)

AF:

0.0596

AC:

125

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

422

844

1265

1687

2109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0398

Hom.:

110

Bravo

AF:

0.0681

Asia WGS

AF:

0.0510

AC:

176

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.055

(source)

DANN

Benign

0.64

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over