Genetic Variant NM_000395.3:c.68G>A (chr22-36922275-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000395.3(CSF2RB):c.68G>A(p.Gly23Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000492 in 1,423,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G23A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

CSF2RB
NM_000395.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.562

Publications

0 publications found

Variant links:

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

CSF2RB links:

ENSG00000304449 (HGNC:):

ENSG00000304449 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.08416775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.68G>A	p.Gly23Glu	missense_variant	Exon 2 of 14	ENST00000403662.8	NP_000386.1	P32927-1Q6NSJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8 link	c.68G>A	p.Gly23Glu	missense_variant	Exon 2 of 14	5	NM_000395.3	ENSP00000384053.3		P32927-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000492

AC:

AN:

1423636

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704598

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32772

American (AMR)

AF:

0.00

AC:

AN:

39454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25346

East Asian (EAS)

AF:

0.000185

AC:

AN:

37904

South Asian (SAS)

AF:

0.00

AC:

AN:

81108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50648

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4620

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092928

Other (OTH)

AF:

0.00

AC:

AN:

58856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.2

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.36

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.42

T;T;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.4

L;.;L

PhyloP100

0.56

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.76

T;T;T

Sift4G

Benign

0.97

T;T;T

Polyphen

0.26

B;.;B

Vest4

0.092

MutPred

0.46

Gain of disorder (P = 0.0504);Gain of disorder (P = 0.0504);Gain of disorder (P = 0.0504);

MVP

0.60

MPC

0.22

ClinPred

0.095

GERP RS

-2.2

PromoterAI

0.042

Neutral

(source)

Varity_R

0.038

gMVP

0.30

Mutation Taster

=97/3

polymorphism

(source)

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

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NM_000395.3:c.68G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over