rs117805308

Positions:

• chr22-36930752-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.388

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=0.004304707).
• 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	c.934G>A	p.Asp312Asn	missense_variant	8/14	ENST00000403662.8	NP_000386.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1929 AN: 152104 Hom.: 14 Cov.: 32

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.: 29 AF XY: 0.0126 AC XY: 1706 AN XY: 135866

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.: 34 AF XY: 0.0167 AC XY: 12159 AN XY: 727132

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.: 14 Cov.: 32 AF XY: 0.0121 AC XY: 904 AN XY: 74412

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.: 37

Bravo AF: 0.0116

TwinsUK AF: 0.0221 AC: 82

ALSPAC AF: 0.0205 AC: 79

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.0205 AC: 176

ExAC AF: 0.0132 AC: 1597

Asia WGS AF: 0.00231 AC: 8 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

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	T
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	N
LIST_S2	Benign	0.70	T;T;T
MetaRNN	Benign	0.0043	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.74	N;.;.
PrimateAI	Benign	0.32	T
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	T
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

Other links and lift over

dbSNP: rs117805308; hg19: chr22-37326794;