22-36926778-T-G

Variant names:

• chr22-36926778-T-G
• rs17811365
• NM_000395.3:c.391+601T>G

Variant summary

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

The NM_000395.3(CSF2RB):​c.391+601T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 152,230 control chromosomes in the GnomAD database, including 709 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 0.094 (709 hom., cov: 33)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 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.391+601T>G		intron	N/A	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.391+601T>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.391+601T>G		intron	N/A	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000406230.5	TSL:1	c.391+601T>G		intron	N/A	ENSP00000385271.1	P32927-2
	CSF2RB	ENST00000910856.1		c.391+601T>G		intron	N/A	ENSP00000580915.1

Frequencies

GnomAD3 genomes AF: 0.0944 AC: 14358 AN: 152112 Hom.: 709 Cov.: 33

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.0867

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

GnomAD4 genome AF: 0.0944 AC: 14367 AN: 152230 Hom.: 709 Cov.: 33 AF XY: 0.0955 AC XY: 7111 AN XY: 74432

African (AFR) AF: 0.0996 AC: 4136 AN: 41534

American (AMR) AF: 0.0815 AC: 1248 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3468

East Asian (EAS) AF: 0.149 AC: 775 AN: 5188

South Asian (SAS) AF: 0.136 AC: 658 AN: 4824

European-Finnish (FIN) AF: 0.0689 AC: 730 AN: 10596

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0917 AC: 6233 AN: 68000

Other (OTH) AF: 0.0886 AC: 187 AN: 2110

Alfa AF: 0.0947 Hom.: 2169

Bravo AF: 0.0936

Asia WGS AF: 0.129 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.041
DANN	Benign	0.71
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: rs17811365; hg19: chr22-37322820;