rs1801122

Positions:

• chr22-36937615-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000395.3(CSF2RB):​c.1807C>A​(p.Pro603Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,572,632 control chromosomes in the GnomAD database, including 1,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.030 (101 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1239 hom.)
• Consequence: CSF2RB NM_000395.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.00

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 (MetaRNN=0.0054210126).
• BP6: Variant 22-36937615-C-A is Benign according to our data. Variant chr22-36937615-C-A is described in ClinVar as [Benign]. Clinvar id is 504754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36937615-C-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0301 (4587/152284) while in subpopulation NFE AF= 0.0446 (3034/68000). AF 95% confidence interval is 0.0433. There are 101 homozygotes in gnomad4. There are 2260 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 101 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.1807C>A	p.Pro603Thr	missense_variant	14/14	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.1807C>A	p.Pro603Thr	missense_variant	14/14	5	NM_000395.3	ENSP00000384053	P1
CSF2RB	ENST00000406230.5	c.1825C>A	p.Pro609Thr	missense_variant	13/13	1		ENSP00000385271

Frequencies

GnomAD3 genomes AF: 0.0301 AC: 4586 AN: 152166 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.00692

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0529

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0446

Gnomad OTH AF: 0.0258

GnomAD3 exomes AF: 0.0318 AC: 5679 AN: 178744 Hom.: 121 AF XY: 0.0334 AC XY: 3239 AN XY: 96890

Gnomad AFR exome AF: 0.00559

Gnomad AMR exome AF: 0.0136

Gnomad ASJ exome AF: 0.0227

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0291

Gnomad FIN exome AF: 0.0529

Gnomad NFE exome AF: 0.0445

Gnomad OTH exome AF: 0.0322

GnomAD4 exome AF: 0.0399 AC: 56717 AN: 1420348 Hom.: 1239 Cov.: 35 AF XY: 0.0399 AC XY: 28009 AN XY: 702762

Gnomad4 AFR exome AF: 0.00563

Gnomad4 AMR exome AF: 0.0140

Gnomad4 ASJ exome AF: 0.0238

Gnomad4 EAS exome AF: 0.0000536

Gnomad4 SAS exome AF: 0.0284

Gnomad4 FIN exome AF: 0.0566

Gnomad4 NFE exome AF: 0.0440

Gnomad4 OTH exome AF: 0.0347

GnomAD4 genome AF: 0.0301 AC: 4587 AN: 152284 Hom.: 101 Cov.: 32 AF XY: 0.0304 AC XY: 2260 AN XY: 74462

Gnomad4 AFR AF: 0.00690

Gnomad4 AMR AF: 0.0236

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0284

Gnomad4 FIN AF: 0.0529

Gnomad4 NFE AF: 0.0446

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0386 Hom.: 188

Bravo AF: 0.0265

TwinsUK AF: 0.0405 AC: 150

ALSPAC AF: 0.0433 AC: 167

ESP6500AA AF: 0.00516 AC: 22

ESP6500EA AF: 0.0364 AC: 305

ExAC AF: 0.0255 AC: 3001

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 21205713, 20981092, 9410898, 27884173) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 26, 2014

p.Pro603Thr in exon 14 of CSF2RB: This variant is not expected to have clinical significance because it has been identified in 3.6% (305/8368) of European Ameri can chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington. edu/EVS/; dbSNP rs1801122). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Uncertain	0.010
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.78	T;T;T
MetaRNN	Benign	0.0054	T;T;T
MetaSVM	Uncertain	0.42	D
MutationAssessor	Benign	1.9	L;.;.
MutationTaster	Benign	0.93	D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.064
MPC		0.50
ClinPred		0.011	T
GERP RS		5.4
Varity_R		0.19
gMVP		0.34

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: rs1801122; hg19: chr22-37333657;