Genetic Variant CSF2RB:c.-75C>T (chr22-36922133-C-T) – 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.-75C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 1,371,378 control chromosomes in the GnomAD database, including 1,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 129 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1396 hom. )

Consequence

CSF2RB
NM_000395.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.620

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 links:

ENSG00000304449 (HGNC:):

ENSG00000304449 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=-0.8).

BP6

Variant 22-36922133-C-T is Benign according to our data. Variant chr22-36922133-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1187413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.-75C>T		5_prime_UTR_variant	Exon 2 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.-75C>T		5_prime_UTR_variant	Exon 2 of 14	5	NM_000395.3	ENSP00000384053.3		P32927-1

Frequencies

GnomAD3 genomes

AF:

0.0366

AC:

5566

AN:

152182

Hom.:

129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.0637

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.0383

Gnomad SAS

AF:

0.0517

Gnomad FIN

AF:

0.0515

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0448

Gnomad OTH

AF:

0.0449

GnomAD4 exome

AF:

0.0450

AC:

54851

AN:

1219078

Hom.:

1396

Cov.:

AF XY:

0.0455

AC XY:

27686

AN XY:

608144

show subpopulations

African (AFR)

AF:

0.0146

AC:

412

AN:

28174

American (AMR)

AF:

0.0228

AC:

806

AN:

35410

Ashkenazi Jewish (ASJ)

AF:

0.0247

AC:

596

AN:

24120

East Asian (EAS)

AF:

0.0374

AC:

1305

AN:

34858

South Asian (SAS)

AF:

0.0520

AC:

3937

AN:

75678

European-Finnish (FIN)

AF:

0.0517

AC:

2145

AN:

41456

Middle Eastern (MID)

AF:

0.0509

AC:

193

AN:

3790

European-Non Finnish (NFE)

AF:

0.0467

AC:

43172

AN:

923640

Other (OTH)

AF:

0.0440

AC:

2285

AN:

51952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2682

5364

8046

10728

13410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0366

AC:

5569

AN:

152300

Hom.:

129

Cov.:

AF XY:

0.0370

AC XY:

2752

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0177

AC:

735

AN:

41562

American (AMR)

AF:

0.0344

AC:

526

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3472

East Asian (EAS)

AF:

0.0384

AC:

199

AN:

5178

South Asian (SAS)

AF:

0.0520

AC:

251

AN:

4830

European-Finnish (FIN)

AF:

0.0515

AC:

547

AN:

10626

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0448

AC:

3047

AN:

68006

Other (OTH)

AF:

0.0454

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

285

570

855

1140

1425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0344

Hom.:

Bravo

AF:

0.0337

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

ClinVar

Significance: Likely 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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 10, 2019

GeneDx

Significance:Likely 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

-0.80

CADD

Benign

(source)

DANN

Benign

0.38

PhyloP100

0.62

PromoterAI

-0.0061

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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22-36922133-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over