rs2075936

Variant names:

• chr22-36932709-A-G
• rs2075936
• NM_000395.3:c.1013-56A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-36932709-A-G
• chr22-36932709-A-C
• chr22-36932709-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000395.3(CSF2RB):​c.1013-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,589,592 control chromosomes in the GnomAD database, including 182,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15846 hom., cov: 31)
  • Exomes 𝑓: 0.47 (167145 hom.)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0590
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-36932709-A-G is Benign according to our data. Variant chr22-36932709-A-G is described in ClinVar as Benign. ClinVar VariationId is 1275163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 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.1013-56A>G		intron	N/A	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.1031-56A>G		intron	N/A	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.1013-56A>G		intron	N/A	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000406230.5	TSL:1	c.1031-56A>G		intron	N/A	ENSP00000385271.1	P32927-2
	CSF2RB	ENST00000910856.1		c.1013-56A>G		intron	N/A	ENSP00000580915.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65562 AN: 151808 Hom.: 15817 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.474 AC: 681840 AN: 1437666 Hom.: 167145 AF XY: 0.473 AC XY: 337301 AN XY: 713562

African (AFR) AF: 0.228 AC: 7589 AN: 33264

American (AMR) AF: 0.664 AC: 27778 AN: 41856

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 12480 AN: 25610

East Asian (EAS) AF: 0.834 AC: 32791 AN: 39310

South Asian (SAS) AF: 0.437 AC: 36464 AN: 83472

European-Finnish (FIN) AF: 0.588 AC: 28746 AN: 48924

Middle Eastern (MID) AF: 0.388 AC: 1909 AN: 4914

European-Non Finnish (NFE) AF: 0.460 AC: 506187 AN: 1100730

Other (OTH) AF: 0.468 AC: 27896 AN: 59586

GnomAD4 genome AF: 0.432 AC: 65636 AN: 151926 Hom.: 15846 Cov.: 31 AF XY: 0.443 AC XY: 32862 AN XY: 74234

African (AFR) AF: 0.237 AC: 9838 AN: 41470

American (AMR) AF: 0.536 AC: 8186 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1703 AN: 3468

East Asian (EAS) AF: 0.797 AC: 4107 AN: 5154

South Asian (SAS) AF: 0.464 AC: 2231 AN: 4804

European-Finnish (FIN) AF: 0.604 AC: 6361 AN: 10528

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.470 AC: 31885 AN: 67910

Other (OTH) AF: 0.438 AC: 923 AN: 2108

Alfa AF: 0.439 Hom.: 33336

Bravo AF: 0.424

Asia WGS AF: 0.605 AC: 2099 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.72
PhyloP100		0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2075936; hg19: chr22-37328751; COSMIC: COSV53261544; COSMIC: COSV53261544;