Genetic Variant CSF2RB:p.Val652Leu (chr22-36937762-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000395.3(CSF2RB):c.1954G>T(p.Val652Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,354 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. V652M) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CSF2RB
NM_000395.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05725485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3 link	c.1954G>T	p.Val652Leu	missense_variant	Exon 14 of 14	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8 link	c.1954G>T	p.Val652Leu	missense_variant	Exon 14 of 14	5	NM_000395.3	ENSP00000384053.3
CSF2RB	ENST00000406230.5 link	c.1972G>T	p.Val658Leu	missense_variant	Exon 13 of 13	1		ENSP00000385271.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1422354

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32812

American (AMR)

AF:

0.00

AC:

AN:

37404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25380

East Asian (EAS)

AF:

0.00

AC:

AN:

37954

South Asian (SAS)

AF:

0.00

AC:

AN:

82096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

9.16e-7

AC:

AN:

1091868

Other (OTH)

AF:

0.00

AC:

AN:

58906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

0.10

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.030

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.24

T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.33

T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.057

T;T;T

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.0

L;.;.

PhyloP100

-1.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.39

N;.;N

REVEL

Benign

0.27

Sift

Benign

0.30

T;.;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.019

B;.;B

Vest4

0.067

MutPred

0.15

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;

MVP

0.58

MPC

0.15

ClinPred

0.093

GERP RS

-7.8

Varity_R

0.024

gMVP

0.075

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over