rs1801116

Variant names:

• chr22-36938208-G-A
• rs1801116
• NM_000395.3:c.2400G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000395.3(CSF2RB):​c.2400G>A​(p.Pro800Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,614,078 control chromosomes in the GnomAD database, including 710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (44 hom., cov: 32)
  • Exomes 𝑓: 0.028 (666 hom.)
• Consequence: CSF2RB NM_000395.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.287

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 22-36938208-G-A is Benign according to our data. Variant chr22-36938208-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 226552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.287 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0231 (3514/152224) while in subpopulation NFE AF= 0.0282 (1917/67990). AF 95% confidence interval is 0.0271. There are 44 homozygotes in gnomad4. There are 1683 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.2400G>A	p.Pro800Pro	synonymous_variant	Exon 14 of 14	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.2400G>A	p.Pro800Pro	synonymous_variant	Exon 14 of 14	5	NM_000395.3	ENSP00000384053.3
CSF2RB	ENST00000406230.5	c.2418G>A	p.Pro806Pro	synonymous_variant	Exon 13 of 13	1		ENSP00000385271.1

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3512 AN: 152106 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0245

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0282

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0229 AC: 5758 AN: 251372 Hom.: 89 AF XY: 0.0236 AC XY: 3201 AN XY: 135864

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.0309

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0219

Gnomad FIN exome AF: 0.0272

Gnomad NFE exome AF: 0.0294

Gnomad OTH exome AF: 0.0299

GnomAD4 exome AF: 0.0284 AC: 41549 AN: 1461854 Hom.: 666 Cov.: 35 AF XY: 0.0284 AC XY: 20685 AN XY: 727226

Gnomad4 AFR exome AF: 0.0162

Gnomad4 AMR exome AF: 0.0111

Gnomad4 ASJ exome AF: 0.0332

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0230

Gnomad4 FIN exome AF: 0.0280

Gnomad4 NFE exome AF: 0.0308

Gnomad4 OTH exome AF: 0.0260

GnomAD4 genome AF: 0.0231 AC: 3514 AN: 152224 Hom.: 44 Cov.: 32 AF XY: 0.0226 AC XY: 1683 AN XY: 74422

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.0245

Gnomad4 NFE AF: 0.0282

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0275 Hom.: 31

Bravo AF: 0.0220

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0293

EpiControl AF: 0.0291

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Pro800Pro in exon 14 of CSF2RB: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 2.8% (245/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1801116). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs1801116; hg19: chr22-37334250;