Genetic Variant CSF2RB:c.1153-198T>C (chr22-36933634-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000395.3(CSF2RB):c.1153-198T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,096 control chromosomes in the GnomAD database, including 5,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 5086 hom., cov: 32)

Consequence

CSF2RB
NM_000395.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.534

Publications

9 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 22-36933634-T-C is Benign according to our data. Variant chr22-36933634-T-C is described in ClinVar as Benign. ClinVar VariationId is 1276886.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.1153-198T>C		intron_variant	Intron 9 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.1153-198T>C		intron_variant	Intron 9 of 13	5	NM_000395.3	ENSP00000384053.3		P32927-1
CSF2RB	ENST00000406230.5 link	c.1171-198T>C		intron_variant	Intron 8 of 12	1		ENSP00000385271.1		P32927-2

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38076

AN:

151978

Hom.:

5087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.0683

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.250

AC:

38087

AN:

152096

Hom.:

5086

Cov.:

AF XY:

0.242

AC XY:

17978

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.319

AC:

13214

AN:

41454

American (AMR)

AF:

0.179

AC:

2744

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

745

AN:

3466

East Asian (EAS)

AF:

0.0680

AC:

352

AN:

5174

South Asian (SAS)

AF:

0.235

AC:

1135

AN:

4822

European-Finnish (FIN)

AF:

0.164

AC:

1735

AN:

10596

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.254

AC:

17258

AN:

67972

Other (OTH)

AF:

0.258

AC:

544

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1457

2915

4372

5830

7287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.253

Hom.:

7977

Bravo

AF:

0.255

Asia WGS

AF:

0.137

AC:

481

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 22, 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

-1.0

CADD

Benign

0.042

(source)

DANN

Benign

0.17

PhyloP100

-0.53

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over