chr22-36922267-C-A

Variant names:

• chr22-36922267-C-A
• rs200588212
• NM_000395.3:c.60C>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000395.3(CSF2RB):​c.60C>A​(p.Ser20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,578,894 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (3 hom.)
• Consequence: CSF2RB NM_000395.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.40
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• surfactant metabolism dysfunction, pulmonary, 5

  Inheritance: AR Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000304449 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041003227).
• BP6: Variant 22-36922267-C-A is Benign according to our data. Variant chr22-36922267-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1168184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000395.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	NM_000395.3	MANE Select	c.60C>A	p.Ser20Arg	missense	Exon 2 of 14	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.60C>A	p.Ser20Arg	missense	Exon 2 of 14	NP_001397756.1	P32927-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.60C>A	p.Ser20Arg	missense	Exon 2 of 14	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000406230.5	TSL:1	c.60C>A	p.Ser20Arg	missense	Exon 1 of 13	ENSP00000385271.1	P32927-2
	CSF2RB	ENST00000910856.1		c.60C>A	p.Ser20Arg	missense	Exon 2 of 14	ENSP00000580915.1

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 55 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00945

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000985 AC: 188 AN: 190856 AF XY: 0.000918

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000698

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0124

Gnomad FIN exome AF: 0.0000597

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.000400

GnomAD4 exome AF: 0.000289 AC: 412 AN: 1426626 Hom.: 3 Cov.: 31 AF XY: 0.000266 AC XY: 188 AN XY: 706382

African (AFR) AF: 0.00 AC: 0 AN: 32894

American (AMR) AF: 0.0000501 AC: 2 AN: 39942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25386

East Asian (EAS) AF: 0.00885 AC: 337 AN: 38080

South Asian (SAS) AF: 0.0000492 AC: 4 AN: 81360

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4560

European-Non Finnish (NFE) AF: 0.0000283 AC: 31 AN: 1094608

Other (OTH) AF: 0.000627 AC: 37 AN: 58978

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152268 Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00947 AC: 49 AN: 5172

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68000

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.0000439 Hom.: 0

Bravo AF: 0.000434

ExAC AF: 0.000700 AC: 84

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CSF2RB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.020
DANN	Benign	0.41
DEOGEN2	Benign	0.31	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.1	L
PhyloP100		-2.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.16
Sift	Benign	0.72	T
Sift4G	Benign	0.60	T
Polyphen		0.0030	B
Vest4		0.11
MutPred		0.26		Loss of glycosylation at S20 (P = 0.0586)
MVP		0.56
MPC		0.17
ClinPred		0.0057	T
GERP RS		-6.8
PromoterAI		-0.015	Neutral
Varity_R		0.043
gMVP		0.44
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs200588212; hg19: chr22-37318309;