chr22-36914004-G-A

Variant names:

• chr22-36914004-G-A
• rs2075726
• NM_000395.3:c.-173+327G>A

Variant summary

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

The NM_000395.3(CSF2RB):​c.-173+327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,722 control chromosomes in the GnomAD database, including 15,250 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 0.43 (15250 hom., cov: 29)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840
• Publications: 11 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 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.-173+327G>A		intron	N/A	NP_000386.1
	CSF2RB	NM_001410827.1		c.-173+327G>A		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.-173+327G>A		intron	N/A	ENSP00000384053.3
	ENSG00000304449	ENST00000803517.1		n.233-1728C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64703 AN: 151604 Hom.: 15247 Cov.: 29

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.427 AC: 64723 AN: 151722 Hom.: 15250 Cov.: 29 AF XY: 0.431 AC XY: 31966 AN XY: 74118

African (AFR) AF: 0.216 AC: 8952 AN: 41382

American (AMR) AF: 0.500 AC: 7636 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3466

East Asian (EAS) AF: 0.571 AC: 2925 AN: 5124

South Asian (SAS) AF: 0.439 AC: 2109 AN: 4800

European-Finnish (FIN) AF: 0.515 AC: 5426 AN: 10544

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34178 AN: 67836

Other (OTH) AF: 0.446 AC: 942 AN: 2110

Alfa AF: 0.482 Hom.: 79015

Bravo AF: 0.415

Asia WGS AF: 0.509 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.41
DANN	Benign	0.84
PhyloP100		-0.84
PromoterAI		0.026	Neutral
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: rs2075726; hg19: chr22-37310046;