rs16846

Variant names:

• chr22-36929791-C-T
• rs16846
• NM_000395.3:c.702C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BA1

The NM_000395.3(CSF2RB):​c.702C>T​(p.Cys234Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,613,734 control chromosomes in the GnomAD database, including 1,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (194 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1115 hom.)
• Consequence: CSF2RB NM_000395.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0170
• Publications: 7 publications found

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: DEFINITIVE, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 22-36929791-C-T is Benign according to our data. Variant chr22-36929791-C-T is described in ClinVar as Benign. ClinVar VariationId is 226554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0761 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000395.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	NM_000395.3	MANE Select	c.702C>T	p.Cys234Cys	synonymous	Exon 6 of 14	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.702C>T	p.Cys234Cys	synonymous	Exon 6 of 14	NP_001397756.1	P32927-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.702C>T	p.Cys234Cys	synonymous	Exon 6 of 14	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000406230.5	TSL:1	c.702C>T	p.Cys234Cys	synonymous	Exon 5 of 13	ENSP00000385271.1	P32927-2
	CSF2RB	ENST00000910856.1		c.702C>T	p.Cys234Cys	synonymous	Exon 6 of 14	ENSP00000580915.1

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6926 AN: 152188 Hom.: 193 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.0518

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.0578

GnomAD2 exomes AF: 0.0324 AC: 8058 AN: 248422 AF XY: 0.0325

Gnomad AFR exome AF: 0.0763

Gnomad AMR exome AF: 0.0275

Gnomad ASJ exome AF: 0.0265

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00977

Gnomad NFE exome AF: 0.0407

Gnomad OTH exome AF: 0.0496

GnomAD4 exome AF: 0.0347 AC: 50686 AN: 1461428 Hom.: 1115 Cov.: 32 AF XY: 0.0348 AC XY: 25274 AN XY: 727012

African (AFR) AF: 0.0815 AC: 2727 AN: 33472

American (AMR) AF: 0.0301 AC: 1342 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 670 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39690

South Asian (SAS) AF: 0.0181 AC: 1561 AN: 86226

European-Finnish (FIN) AF: 0.0107 AC: 571 AN: 53276

Middle Eastern (MID) AF: 0.140 AC: 808 AN: 5758

European-Non Finnish (NFE) AF: 0.0366 AC: 40655 AN: 1111838

Other (OTH) AF: 0.0389 AC: 2350 AN: 60384

GnomAD4 genome AF: 0.0455 AC: 6935 AN: 152306 Hom.: 194 Cov.: 32 AF XY: 0.0441 AC XY: 3283 AN XY: 74488

African (AFR) AF: 0.0783 AC: 3255 AN: 41572

American (AMR) AF: 0.0428 AC: 656 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4830

European-Finnish (FIN) AF: 0.0102 AC: 108 AN: 10620

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0371 AC: 2524 AN: 68006

Other (OTH) AF: 0.0568 AC: 120 AN: 2114

Alfa AF: 0.0426 Hom.: 90

Bravo AF: 0.0495

Asia WGS AF: 0.0200 AC: 73 AN: 3478

EpiCase AF: 0.0502

EpiControl AF: 0.0454

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.54
PhyloP100		0.017
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.53		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.53		Position offset: -6

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

Other links and lift over

dbSNP: rs16846; hg19: chr22-37325833;