rs131840

Variant names:

• chr22-36937752-A-G
• rs131840
• NM_000395.3:c.1944A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-36937752-A-G
• chr22-36937752-A-C
• chr22-36937752-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000395.3(CSF2RB):​c.1944A>G​(p.Pro648Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,569,224 control chromosomes in the GnomAD database, including 522,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46289 hom., cov: 31)
  • Exomes 𝑓: 0.82 (476086 hom.)
• Consequence: CSF2RB NM_000395.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.270
• Publications: 24 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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 22-36937752-A-G is Benign according to our data. Variant chr22-36937752-A-G is described in ClinVar as Benign. ClinVar VariationId is 226549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

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.1944A>G	p.Pro648Pro	synonymous	Exon 14 of 14	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.1962A>G	p.Pro654Pro	synonymous	Exon 14 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.1944A>G	p.Pro648Pro	synonymous	Exon 14 of 14	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000406230.5	TSL:1	c.1962A>G	p.Pro654Pro	synonymous	Exon 13 of 13	ENSP00000385271.1	P32927-2
	CSF2RB	ENST00000910856.1		c.1980A>G	p.Pro660Pro	synonymous	Exon 14 of 14	ENSP00000580915.1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117655 AN: 151950 Hom.: 46252 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.776

GnomAD2 exomes AF: 0.833 AC: 149507 AN: 179536 AF XY: 0.834

Gnomad AFR exome AF: 0.634

Gnomad AMR exome AF: 0.886

Gnomad ASJ exome AF: 0.784

Gnomad EAS exome AF: 0.944

Gnomad FIN exome AF: 0.867

Gnomad NFE exome AF: 0.809

Gnomad OTH exome AF: 0.817

GnomAD4 exome AF: 0.818 AC: 1159801 AN: 1417156 Hom.: 476086 Cov.: 87 AF XY: 0.819 AC XY: 574293 AN XY: 700912

African (AFR) AF: 0.625 AC: 20345 AN: 32566

American (AMR) AF: 0.879 AC: 32521 AN: 36990

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 19979 AN: 25316

East Asian (EAS) AF: 0.945 AC: 35399 AN: 37456

South Asian (SAS) AF: 0.865 AC: 70570 AN: 81570

European-Finnish (FIN) AF: 0.866 AC: 43197 AN: 49898

Middle Eastern (MID) AF: 0.766 AC: 4362 AN: 5692

European-Non Finnish (NFE) AF: 0.813 AC: 885586 AN: 1088962

Other (OTH) AF: 0.815 AC: 47842 AN: 58706

GnomAD4 genome AF: 0.774 AC: 117750 AN: 152068 Hom.: 46289 Cov.: 31 AF XY: 0.779 AC XY: 57930 AN XY: 74338

African (AFR) AF: 0.638 AC: 26454 AN: 41486

American (AMR) AF: 0.822 AC: 12559 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2724 AN: 3472

East Asian (EAS) AF: 0.940 AC: 4827 AN: 5136

South Asian (SAS) AF: 0.876 AC: 4227 AN: 4826

European-Finnish (FIN) AF: 0.861 AC: 9141 AN: 10614

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55278 AN: 67932

Other (OTH) AF: 0.777 AC: 1642 AN: 2112

Alfa AF: 0.799 Hom.: 68521

Bravo AF: 0.767

Asia WGS AF: 0.866 AC: 3013 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.18
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs131840; hg19: chr22-37333794; COSMIC: COSV53256516;