22-36937402-AG-TC

Variant names:

• chr22-36937402-AG-TC
• NM_000395.3:c.1594_1595delAGinsTC
• CSF2RB p.533

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_000395.3(CSF2RB):​c.1594_1595delAGinsTC​(p.533) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S532S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSF2RB NM_000395.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 0 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=1.96 with no splicing effect.

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.1594_1595delAGinsTC	p.533	synonymous	N/A	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.1612_1613delAGinsTC	p.539	synonymous	N/A	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.1594_1595delAGinsTC	p.533	synonymous	N/A	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000406230.5	TSL:1	c.1612_1613delAGinsTC	p.539	synonymous	N/A	ENSP00000385271.1	P32927-2
	CSF2RB	ENST00000910856.1		c.1630_1631delAGinsTC	p.545	synonymous	N/A	ENSP00000580915.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-37333444;