Genetic Variant CSF2RB:c.-172-45C>T (chr22-36921991-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_StrongBS1BS2

The NM_000395.3(CSF2RB):c.-172-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 598,760 control chromosomes in the GnomAD database, including 598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 119 hom., cov: 33)

Exomes 𝑓: 0.041 ( 479 hom. )

Consequence

CSF2RB
NM_000395.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.10

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=-0.9).

BP6

Variant 22-36921991-C-T is Benign according to our data. Variant chr22-36921991-C-T is described in ClinVar as [Benign]. Clinvar id is 1283425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0318 (4841/152292) while in subpopulation NFE AF = 0.0484 (3292/68008). AF 95% confidence interval is 0.047. There are 119 homozygotes in GnomAd4. There are 2289 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 119 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.-172-45C>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.-172-45C>T		intron_variant	Intron 1 of 13	5	NM_000395.3	ENSP00000384053.3		P32927-1

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4844

AN:

152174

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00874

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0404

Gnomad FIN

AF:

0.0338

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0484

Gnomad OTH

AF:

0.0387

GnomAD4 exome

AF:

0.0413

AC:

18461

AN:

446468

Hom.:

479

Cov.:

AF XY:

0.0421

AC XY:

9868

AN XY:

234246

show subpopulations

African (AFR)

AF:

0.00800

AC:

101

AN:

12620

American (AMR)

AF:

0.0230

AC:

466

AN:

20274

Ashkenazi Jewish (ASJ)

AF:

0.0276

AC:

378

AN:

13714

East Asian (EAS)

AF:

0.000130

AC:

AN:

30860

South Asian (SAS)

AF:

0.0478

AC:

2234

AN:

46694

European-Finnish (FIN)

AF:

0.0348

AC:

1027

AN:

29484

Middle Eastern (MID)

AF:

0.0475

AC:

AN:

1958

European-Non Finnish (NFE)

AF:

0.0496

AC:

13144

AN:

265014

Other (OTH)

AF:

0.0392

AC:

1014

AN:

25850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

874

1748

2623

3497

4371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0318

AC:

4841

AN:

152292

Hom.:

119

Cov.:

AF XY:

0.0307

AC XY:

2289

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00871

AC:

362

AN:

41556

American (AMR)

AF:

0.0214

AC:

328

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.0404

AC:

195

AN:

4828

European-Finnish (FIN)

AF:

0.0338

AC:

359

AN:

10616

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0484

AC:

3292

AN:

68008

Other (OTH)

AF:

0.0383

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

241

482

722

963

1204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0464

Hom.:

Bravo

AF:

0.0301

Asia WGS

AF:

0.0140

AC:

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 27, 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

-0.90

CADD

Benign

0.42

(source)

DANN

Benign

0.54

PhyloP100

-1.1

PromoterAI

-0.11

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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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22-36921991-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