NM_000395.3:c.68G>C

Variant names:

• chr22-36922275-G-C
• rs866832522
• NM_000395.3:c.68G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000395.3(CSF2RB):​c.68G>C​(p.Gly23Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G23G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSF2RB NM_000395.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.562
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000304449 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17641875).

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.68G>C	p.Gly23Ala	missense	Exon 2 of 14	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.68G>C	p.Gly23Ala	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.68G>C	p.Gly23Ala	missense	Exon 2 of 14	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000406230.5	TSL:1	c.68G>C	p.Gly23Ala	missense	Exon 1 of 13	ENSP00000385271.1	P32927-2
	CSF2RB	ENST00000910856.1		c.68G>C	p.Gly23Ala	missense	Exon 2 of 14	ENSP00000580915.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.3
DANN	Benign	0.95
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.56
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.29
Sift	Benign	0.23	T
Sift4G	Benign	0.32	T
Polyphen		0.92	P
Vest4		0.22
MutPred		0.41		Loss of loop (P = 0.0986)
MVP		0.80
MPC		0.32
ClinPred		0.19	T
GERP RS		-2.2
PromoterAI		0.11	Neutral
Varity_R		0.041
gMVP		0.40
Mutation Taster		=95/5	polymorphism

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: rs866832522; hg19: chr22-37318317;