NM_000395.3:c.1153-13T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000395.3(CSF2RB):c.1153-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00668 in 1,602,758 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 16 hom., cov: 31)

Exomes 𝑓: 0.0065 ( 163 hom. )

Consequence

CSF2RB
NM_000395.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.197

Publications

2 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=-0.91).

BP6

Variant 22-36933819-T-C is Benign according to our data. Variant chr22-36933819-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00846 (1287/152114) while in subpopulation SAS AF = 0.051 (245/4804). AF 95% confidence interval is 0.0458. There are 16 homozygotes in GnomAd4. There are 672 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.00844

AC:

1283

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00483

Gnomad SAS

AF:

0.0510

Gnomad FIN

AF:

0.00415

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.0101

AC:

2357

AN:

232220

AF XY:

0.0117

show subpopulations

Gnomad AFR exome

AF:

0.0172

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00685

Gnomad FIN exome

AF:

0.00317

Gnomad NFE exome

AF:

0.00386

Gnomad OTH exome

AF:

0.00884

GnomAD4 exome

AF:

0.00649

AC:

9414

AN:

1450644

Hom.:

163

Cov.:

AF XY:

0.00765

AC XY:

5516

AN XY:

721492

show subpopulations

African (AFR)

AF:

0.0175

AC:

582

AN:

33284

American (AMR)

AF:

0.00326

AC:

144

AN:

44148

Ashkenazi Jewish (ASJ)

AF:

0.000154

AC:

AN:

25994

East Asian (EAS)

AF:

0.00733

AC:

289

AN:

39444

South Asian (SAS)

AF:

0.0458

AC:

3908

AN:

85332

European-Finnish (FIN)

AF:

0.00339

AC:

159

AN:

46838

Middle Eastern (MID)

AF:

0.0115

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.00344

AC:

3818

AN:

1109838

Other (OTH)

AF:

0.00740

AC:

445

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

585

1170

1754

2339

2924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

360

540

720

900

<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:

0.00846

AC:

1287

AN:

152114

Hom.:

Cov.:

AF XY:

0.00904

AC XY:

672

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0170

AC:

705

AN:

41506

American (AMR)

AF:

0.00209

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00484

AC:

AN:

5162

South Asian (SAS)

AF:

0.0510

AC:

245

AN:

4804

European-Finnish (FIN)

AF:

0.00415

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00321

AC:

218

AN:

67954

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

127

191

254

318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00484

Hom.:

Bravo

AF:

0.00802

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

May 30, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

1153-13T>C in intron 9 of CSF2RB: This variant is not expected to have clinical significance because it has been identified in 1.5% (66/4382) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs117405606).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.78

(source)

DANN

Benign

0.63

PhyloP100

-0.20

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over