Genetic Variant CSF2RB:c.-129T>G (chr22-36922079-T-G) – 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.-129T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 805,266 control chromosomes in the GnomAD database, including 317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 50 hom., cov: 33)

Exomes 𝑓: 0.025 ( 267 hom. )

Consequence

CSF2RB
NM_000395.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.27

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=-0.88).

BP6

Variant 22-36922079-T-G is Benign according to our data. Variant chr22-36922079-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1215938.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 = 0.0196 (2988/152250) while in subpopulation SAS AF = 0.0269 (130/4832). AF 95% confidence interval is 0.0249. There are 50 homozygotes in GnomAd4. There are 1493 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.-129T>G		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.-129T>G		5_prime_UTR_variant	Exon 2 of 14	5	NM_000395.3	ENSP00000384053.3		P32927-1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2991

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00459

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.0585

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0271

Gnomad FIN

AF:

0.0354

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0259

Gnomad OTH

AF:

0.0272

GnomAD4 exome

AF:

0.0247

AC:

16141

AN:

653016

Hom.:

267

Cov.:

AF XY:

0.0250

AC XY:

8516

AN XY:

340006

show subpopulations

African (AFR)

AF:

0.00577

AC:

101

AN:

17500

American (AMR)

AF:

0.0152

AC:

509

AN:

33432

Ashkenazi Jewish (ASJ)

AF:

0.0613

AC:

1194

AN:

19486

East Asian (EAS)

AF:

0.0000626

AC:

AN:

31944

South Asian (SAS)

AF:

0.0269

AC:

1684

AN:

62612

European-Finnish (FIN)

AF:

0.0290

AC:

987

AN:

33980

Middle Eastern (MID)

AF:

0.0352

AC:

AN:

2642

European-Non Finnish (NFE)

AF:

0.0257

AC:

10729

AN:

418088

Other (OTH)

AF:

0.0253

AC:

842

AN:

33332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

822

1645

2467

3290

4112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0196

AC:

2988

AN:

152250

Hom.:

Cov.:

AF XY:

0.0201

AC XY:

1493

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00457

AC:

190

AN:

41556

American (AMR)

AF:

0.0160

AC:

245

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0585

AC:

203

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.0269

AC:

130

AN:

4832

European-Finnish (FIN)

AF:

0.0354

AC:

376

AN:

10618

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0259

AC:

1760

AN:

67982

Other (OTH)

AF:

0.0265

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

159

318

478

637

796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.00953

AC:

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

- -

May 26, 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

-0.88

CADD

Benign

0.38

(source)

DANN

Benign

0.43

PhyloP100

-1.3

PromoterAI

0.015

Neutral

(source)

Mutation Taster

=300/0

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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22-36922079-T-G

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