22-36925038-T-C

Variant names:

• chr22-36925038-T-C
• rs2284031
• NM_000395.3:c.201-949T>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.201-949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,090 control chromosomes in the GnomAD database, including 14,542 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 0.40 (14542 hom., cov: 32)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.698
• 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: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 = 0.767 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	NM_000395.3	MANE Select	c.201-949T>C		intron	N/A	NP_000386.1
	CSF2RB	NM_001410827.1		c.201-949T>C		intron	N/A	NP_001397756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.201-949T>C		intron	N/A	ENSP00000384053.3
	CSF2RB	ENST00000406230.5	TSL:1	c.201-949T>C		intron	N/A	ENSP00000385271.1
	CSF2RB	ENST00000421539.1	TSL:5	c.-40-949T>C		intron	N/A	ENSP00000393585.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60963 AN: 151972 Hom.: 14537 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.401 AC: 60984 AN: 152090 Hom.: 14542 Cov.: 32 AF XY: 0.413 AC XY: 30703 AN XY: 74328

African (AFR) AF: 0.153 AC: 6345 AN: 41510

American (AMR) AF: 0.546 AC: 8342 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3470

East Asian (EAS) AF: 0.787 AC: 4068 AN: 5166

South Asian (SAS) AF: 0.454 AC: 2186 AN: 4820

European-Finnish (FIN) AF: 0.591 AC: 6242 AN: 10554

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31192 AN: 67962

Other (OTH) AF: 0.392 AC: 827 AN: 2112

Alfa AF: 0.426 Hom.: 22252

Bravo AF: 0.389

Asia WGS AF: 0.603 AC: 2094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.34
PhyloP100		0.70
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: rs2284031; hg19: chr22-37321080;