chr22-36930752-G-A

Position:

chr22-36930752-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000395.3(CSF2RB):c.934G>A(p.Asp312Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,613,890 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 14 hom., cov: 32)

Exomes 𝑓: 0.017 ( 260 hom. )

Consequence

CSF2RB
NM_000395.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.388

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004304707).

BP6

Variant 22-36930752-G-A is Benign according to our data. Variant chr22-36930752-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 226556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36930752-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0127 (1927/152222) while in subpopulation NFE AF= 0.0211 (1436/68020). AF 95% confidence interval is 0.0202. There are 14 homozygotes in gnomad4. There are 904 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2RB	NM_000395.3 linkuse as main transcript	c.934G>A	p.Asp312Asn	missense_variant	8/14	ENST00000403662.8	NP_000386.1	P32927-1Q6NSJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CSF2RB	ENST00000403662.8 linkuse as main transcript	c.934G>A	p.Asp312Asn	missense_variant	8/14	5	NM_000395.3	ENSP00000384053.3	P32927-1
CSF2RB	ENST00000406230.5 linkuse as main transcript	c.952G>A	p.Asp318Asn	missense_variant	7/13	1		ENSP00000385271.1	P32927-2
CSF2RB	ENST00000421539.1 linkuse as main transcript	c.*8G>A		downstream_gene_variant		5		ENSP00000393585.1	B0QY07

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1929

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0123

AC:

3093

AN:

251242

Hom.:

AF XY:

0.0126

AC XY:

1706

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.00923

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00402

Gnomad FIN exome

AF:

0.0143

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0171

AC:

25053

AN:

1461668

Hom.:

260

Cov.:

AF XY:

0.0167

AC XY:

12159

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00290

Gnomad4 AMR exome

AF:

0.00541

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00424

Gnomad4 FIN exome

AF:

0.0143

Gnomad4 NFE exome

AF:

0.0200

Gnomad4 OTH exome

AF:

0.0165

GnomAD4 genome

AF:

0.0127

AC:

1927

AN:

152222

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

904

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00383

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.0123

Gnomad4 NFE

AF:

0.0211

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0175

Hom.:

Bravo

AF:

0.0116

TwinsUK

AF:

0.0221

AC:

ALSPAC

AF:

0.0205

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0205

AC:

176

ExAC

AF:

0.0132

AC:

1597

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0178

EpiControl

AF:

0.0145

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 12, 2022	See Variant Classification Assertion Criteria. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

Asp312Asn in exon 8 of CSF2RB: This variant is not expected to have clinical sig nificance because it has been identified in 2.0% (176/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs117805308). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.6

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.68

D;T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.70

T;T;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.74

N;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.5

N;.;N

REVEL

Benign

0.12

Sift

Benign

0.51

T;.;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.51

P;.;B

Vest4

0.24

MPC

0.15

ClinPred

0.00057

GERP RS

2.1

Varity_R

0.039

gMVP

0.37

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

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