dbSNP rs131842: CSF2RB:c.*1229A>G (chr22-36939731-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000395.3(CSF2RB):c.*1229A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 160,010 control chromosomes in the GnomAD database, including 11,752 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 11633 hom., cov: 32)

Exomes 𝑓: 0.16 ( 119 hom. )

Consequence

CSF2RB
NM_000395.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.*1229A>G		3_prime_UTR_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.*1229A>G		3_prime_UTR_variant	Exon 14 of 14	5	NM_000395.3	ENSP00000384053.3		P32927-1

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48279

AN:

152066

Hom.:

11603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.677

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.0759

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.274

GnomAD4 exome

AF:

0.157

AC:

1225

AN:

7824

Hom.:

119

Cov.:

AF XY:

0.163

AC XY:

663

AN XY:

4072

show subpopulations

African (AFR)

AF:

0.583

AC:

AN:

108

American (AMR)

AF:

0.152

AC:

252

AN:

1656

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

AN:

East Asian (EAS)

AF:

0.0515

AC:

AN:

602

South Asian (SAS)

AF:

0.239

AC:

219

AN:

916

European-Finnish (FIN)

AF:

0.117

AC:

AN:

120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.146

AC:

591

AN:

4036

Other (OTH)

AF:

0.156

AC:

AN:

282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

100

151

201

251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.318

AC:

48366

AN:

152186

Hom.:

11633

Cov.:

AF XY:

0.311

AC XY:

23182

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.677

AC:

28062

AN:

41460

American (AMR)

AF:

0.213

AC:

3252

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

770

AN:

3468

East Asian (EAS)

AF:

0.0765

AC:

397

AN:

5192

South Asian (SAS)

AF:

0.309

AC:

1492

AN:

4826

European-Finnish (FIN)

AF:

0.126

AC:

1335

AN:

10610

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12228

AN:

68014

Other (OTH)

AF:

0.272

AC:

575

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1295

2590

3884

5179

6474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.216

Hom.:

8730

Bravo

AF:

0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.086

(source)

DANN

Benign

0.43

PhyloP100

-1.5

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

Computational scores

Splicing

Publications

Other links and lift over