Genetic Variant CSF2RB:c.-172-64G>T (chr22-36921972-G-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.-172-64G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 591,026 control chromosomes in the GnomAD database, including 76,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16648 hom., cov: 33)

Exomes 𝑓: 0.51 ( 59561 hom. )

Consequence

CSF2RB
NM_000395.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.04

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=-0.91).

BP6

Variant 22-36921972-G-T is Benign according to our data. Variant chr22-36921972-G-T is described in ClinVar as [Benign]. Clinvar id is 1238097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.-172-64G>T		intron_variant	Intron 1 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.-172-64G>T		intron_variant	Intron 1 of 13	5	NM_000395.3	ENSP00000384053.3		P32927-1

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66742

AN:

151988

Hom.:

16639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.575

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.513

AC:

225329

AN:

438920

Hom.:

59561

AF XY:

0.508

AC XY:

116864

AN XY:

230054

show subpopulations

African (AFR)

AF:

0.190

AC:

2342

AN:

12310

American (AMR)

AF:

0.626

AC:

11844

AN:

18934

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

6872

AN:

13512

East Asian (EAS)

AF:

0.611

AC:

18739

AN:

30660

South Asian (SAS)

AF:

0.406

AC:

18465

AN:

45496

European-Finnish (FIN)

AF:

0.573

AC:

16665

AN:

29104

Middle Eastern (MID)

AF:

0.485

AC:

936

AN:

1928

European-Non Finnish (NFE)

AF:

0.522

AC:

136583

AN:

261474

Other (OTH)

AF:

0.505

AC:

12883

AN:

25502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5321

10641

15962

21282

26603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.439

AC:

66776

AN:

152106

Hom.:

16648

Cov.:

AF XY:

0.445

AC XY:

33110

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.196

AC:

8146

AN:

41512

American (AMR)

AF:

0.578

AC:

8842

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1771

AN:

3470

East Asian (EAS)

AF:

0.575

AC:

2974

AN:

5170

South Asian (SAS)

AF:

0.395

AC:

1908

AN:

4830

European-Finnish (FIN)

AF:

0.563

AC:

5958

AN:

10578

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.524

AC:

35603

AN:

67932

Other (OTH)

AF:

0.450

AC:

952

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1790

3581

5371

7162

8952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.451

Hom.:

5428

Bravo

AF:

0.430

Asia WGS

AF:

0.492

AC:

1708

AN:

3478

ClinVar

Significance: 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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 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

-0.91

CADD

Benign

0.055

(source)

DANN

Benign

0.46

PhyloP100

-2.0

PromoterAI

-0.076

Neutral

(source)

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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22-36921972-G-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