Genetic Variant CSF2RB:c.-172-164C>T (chr22-36921872-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.-172-164C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 152,300 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 242 hom., cov: 33)

Consequence

CSF2RB
NM_000395.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.538

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=-0.86).

BP6

Variant 22-36921872-C-T is Benign according to our data. Variant chr22-36921872-C-T is described in ClinVar as [Benign]. Clinvar id is 1178164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.-172-164C>T		intron_variant	Intron 1 of 13	ENST00000403662.8	NP_000386.1	P32927-1Q6NSJ8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSF2RB	ENST00000403662.8 link	c.-172-164C>T	intron_variant	Intron 1 of 13	5	NM_000395.3	ENSP00000384053.3	P32927-1
ENSG00000304449	ENST00000803517.1 link	n.232+3878G>A	intron_variant	Intron 1 of 1
ENSG00000304449	ENST00000803518.1 link	n.275-2933G>A	intron_variant	Intron 1 of 1
ENSG00000304449	ENST00000803519.1 link	n.261+1427G>A	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0537

AC:

8179

AN:

152182

Hom.:

241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0690

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0400

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.0418

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0518

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0465

Gnomad OTH

AF:

0.0569

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

GnomAD4 genome

AF:

0.0537

AC:

8186

AN:

152300

Hom.:

242

Cov.:

AF XY:

0.0541

AC XY:

4026

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0689

AC:

2862

AN:

41542

American (AMR)

AF:

0.0399

AC:

611

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3472

East Asian (EAS)

AF:

0.0419

AC:

217

AN:

5178

South Asian (SAS)

AF:

0.102

AC:

492

AN:

4828

European-Finnish (FIN)

AF:

0.0518

AC:

550

AN:

10626

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0465

AC:

3162

AN:

68026

Other (OTH)

AF:

0.0572

AC:

121

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

397

794

1190

1587

1984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0530

Hom.:

Bravo

AF:

0.0524

Asia WGS

AF:

0.0560

AC:

195

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

- -

Jun 10, 2019

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

-0.86

CADD

Benign

1.3

(source)

DANN

Benign

0.78

PhyloP100

-0.54

PromoterAI

0.030

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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22-36921872-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over