chr22-36918248-T-C

Variant names:

• chr22-36918248-T-C
• rs4821564
• NM_000395.3:c.-172-3788T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000395.3(CSF2RB):​c.-172-3788T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,052 control chromosomes in the GnomAD database, including 43,239 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (43239 hom., cov: 32)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• Publications: 4 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

ENSG00000304449 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 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.-172-3788T>C		intron	N/A	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.-172-3788T>C		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.-172-3788T>C		intron	N/A	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000910856.1		c.-172-3788T>C		intron	N/A	ENSP00000580915.1
	CSF2RB	ENST00000910857.1		c.-172-3788T>C		intron	N/A	ENSP00000580916.1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114166 AN: 151934 Hom.: 43190 Cov.: 32

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.733

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.752 AC: 114277 AN: 152052 Hom.: 43239 Cov.: 32 AF XY: 0.757 AC XY: 56279 AN XY: 74312

African (AFR) AF: 0.807 AC: 33460 AN: 41468

American (AMR) AF: 0.788 AC: 12045 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2398 AN: 3468

East Asian (EAS) AF: 0.943 AC: 4887 AN: 5180

South Asian (SAS) AF: 0.738 AC: 3565 AN: 4828

European-Finnish (FIN) AF: 0.743 AC: 7838 AN: 10544

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47657 AN: 67968

Other (OTH) AF: 0.736 AC: 1552 AN: 2110

Alfa AF: 0.727 Hom.: 13296

Bravo AF: 0.756

Asia WGS AF: 0.833 AC: 2895 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.77
PhyloP100		-0.87
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: rs4821564; hg19: chr22-37314290;