rs16997510

chr22-36937364-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000395.3(CSF2RB):c.1569-13T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 1,611,906 control chromosomes in the GnomAD database, including 2,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (577 hom., cov: 31)
  • Exomes 𝑓: 0.032 (1506 hom.)
• Consequence: CSF2RB NM_000395.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.86

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-36937364-T-G is Benign according to our data. Variant chr22-36937364-T-G is described in ClinVar as [Benign]. Clinvar id is 226547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.1569-13T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000403662.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.1569-13T>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_000395.3	P1
CSF2RB	ENST00000406230.5	c.1587-13T>G		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9590 AN: 151432 Hom.: 569 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.00526

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0602

GnomAD3 exomes AF: 0.0418 AC: 10385 AN: 248670 Hom.: 476 AF XY: 0.0429 AC XY: 5774 AN XY: 134650

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.0253

Gnomad ASJ exome AF: 0.0326

Gnomad EAS exome AF: 0.00723

Gnomad SAS exome AF: 0.104

Gnomad FIN exome AF: 0.0105

Gnomad NFE exome AF: 0.0250

Gnomad OTH exome AF: 0.0397

GnomAD4 exome AF: 0.0323 AC: 47223 AN: 1460356 Hom.: 1506 Cov.: 32 AF XY: 0.0341 AC XY: 24762 AN XY: 726568

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.0267

Gnomad4 ASJ exome AF: 0.0316

Gnomad4 EAS exome AF: 0.00786

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0119

Gnomad4 NFE exome AF: 0.0244

Gnomad4 OTH exome AF: 0.0392

GnomAD4 genome AF: 0.0635 AC: 9622 AN: 151550 Hom.: 577 Cov.: 31 AF XY: 0.0624 AC XY: 4618 AN XY: 74044

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0368

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.00527

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0239

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0399 Hom.: 70

Bravo AF: 0.0681

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

1569-13T>G in intron 13 of CSF2RB: This variant is not expected to have clinical significance because it has been identified in 15.7% (690/4406) of African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs16997510). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.055
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16997510; hg19: chr22-37333406;