Variant 22-36922267-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000395.3(CSF2RB):c.60C>A(p.Ser20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,578,894 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 3 hom. )

Consequence

CSF2RB
NM_000395.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.40

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 links:

LOC105373023 (HGNC:):

LOC105373023 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041003227).

BP6

Variant 22-36922267-C-A is Benign according to our data. Variant chr22-36922267-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1168184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3 linkuse as main transcript	c.60C>A	p.Ser20Arg	missense_variant	2/14	ENST00000403662.8
LOC105373023	XR_938230.2 linkuse as main transcript	n.195-3328G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8 linkuse as main transcript	c.60C>A	p.Ser20Arg	missense_variant	2/14	5	NM_000395.3	P1	P32927-1
CSF2RB	ENST00000406230.5 linkuse as main transcript	c.60C>A	p.Ser20Arg	missense_variant	1/13	1			P32927-2

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00945

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000985

AC:

188

AN:

190856

Hom.:

AF XY:

0.000918

AC XY:

AN XY:

102398

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000698

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0124

Gnomad SAS exome

AF:

0.0000401

Gnomad FIN exome

AF:

0.0000597

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.000400

GnomAD4 exome

AF:

0.000289

AC:

412

AN:

1426626

Hom.:

Cov.:

AF XY:

0.000266

AC XY:

188

AN XY:

706382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000501

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00885

Gnomad4 SAS exome

AF:

0.0000492

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.0000283

Gnomad4 OTH exome

AF:

0.000627

GnomAD4 genome

AF:

0.000361

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00947

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000213

Hom.:

Bravo

AF:

0.000434

ExAC

AF:

0.000700

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	CSF2RB: BP4, BS1 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -

CSF2RB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.020

DANN

Benign

0.41

DEOGEN2

Benign

0.31

T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.39

T;T;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.1

L;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.11

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.72

T;T;T

Sift4G

Benign

0.60

T;T;T

Polyphen

0.0030

B;.;B

Vest4

0.11

MutPred

0.26

Loss of glycosylation at S20 (P = 0.0586);Loss of glycosylation at S20 (P = 0.0586);Loss of glycosylation at S20 (P = 0.0586);

MVP

0.56

MPC

0.17

ClinPred

0.0057

GERP RS

-6.8

Varity_R

0.043

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over