rs1801114

chr22-36937762-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000395.3(CSF2RB):c.1954G>A(p.Val652Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,574,552 control chromosomes in the GnomAD database, including 1,385 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 Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.055 (443 hom., cov: 32)
  • Exomes 𝑓: 0.026 (942 hom.)
• Consequence: CSF2RB NM_000395.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.05

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001535207).
• BP6: Variant 22-36937762-G-A is Benign according to our data. Variant chr22-36937762-G-A is described in ClinVar as [Benign]. Clinvar id is 226550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.1954G>A	p.Val652Met	missense_variant	14/14	ENST00000403662.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.1954G>A	p.Val652Met	missense_variant	14/14	5	NM_000395.3	P1
CSF2RB	ENST00000406230.5	c.1972G>A	p.Val658Met	missense_variant	13/13	1

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8314 AN: 152102 Hom.: 439 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0676

Gnomad FIN AF: 0.00442

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0506

GnomAD3 exomes AF: 0.0304 AC: 5634 AN: 185336 Hom.: 185 AF XY: 0.0304 AC XY: 3030 AN XY: 99574

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0225

Gnomad ASJ exome AF: 0.0266

Gnomad EAS exome AF: 0.000288

Gnomad SAS exome AF: 0.0572

Gnomad FIN exome AF: 0.00487

Gnomad NFE exome AF: 0.0202

Gnomad OTH exome AF: 0.0294

GnomAD4 exome AF: 0.0255 AC: 36326 AN: 1422332 Hom.: 942 Cov.: 35 AF XY: 0.0261 AC XY: 18363 AN XY: 703938

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.0240

Gnomad4 ASJ exome AF: 0.0262

Gnomad4 EAS exome AF: 0.000211

Gnomad4 SAS exome AF: 0.0556

Gnomad4 FIN exome AF: 0.00617

Gnomad4 NFE exome AF: 0.0208

Gnomad4 OTH exome AF: 0.0309

GnomAD4 genome AF: 0.0548 AC: 8337 AN: 152220 Hom.: 443 Cov.: 32 AF XY: 0.0531 AC XY: 3953 AN XY: 74426

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0676

Gnomad4 FIN AF: 0.00442

Gnomad4 NFE AF: 0.0206

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0272 Hom.: 170

Bravo AF: 0.0597

TwinsUK AF: 0.0216 AC: 80

ALSPAC AF: 0.0239 AC: 92

ESP6500AA AF: 0.134 AC: 588

ESP6500EA AF: 0.0197 AC: 168

ExAC AF: 0.0290 AC: 3453

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

Val652Met in exon 14 of CSF2RB: This variant is not expected to have clinical si gnificance because it has been identified in 13.4% (588/4378) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs1801114). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	0.30
Dann	Benign	0.64
DEOGEN2	Benign	0.24	T;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.34	T;T;T
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.0	L;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.13	N;.;N
REVEL	Benign	0.22
Sift	Benign	0.27	T;.;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.019	B;.;B
Vest4		0.039
MPC		0.15
ClinPred		0.0022	T
GERP RS		-7.8
Varity_R		0.017
gMVP		0.075

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

Other links and lift over

dbSNP: rs1801114; hg19: chr22-37333804;