chr22-36939731-A-G

Variant names:

• chr22-36939731-A-G
• rs131842
• NM_000395.3:c.*1229A>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.*1229A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 160,010 control chromosomes in the GnomAD database, including 11,752 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 0.32 (11633 hom., cov: 32)
  • Exomes 𝑓: 0.16 (119 hom.)
• Consequence: CSF2RB NM_000395.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 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.*1229A>G		3_prime_UTR	Exon 14 of 14	NP_000386.1
	CSF2RB	NM_001410827.1		c.*1229A>G		3_prime_UTR	Exon 14 of 14	NP_001397756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.*1229A>G		3_prime_UTR	Exon 14 of 14	ENSP00000384053.3

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48279 AN: 152066 Hom.: 11603 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0759

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.157 AC: 1225 AN: 7824 Hom.: 119 Cov.: 0 AF XY: 0.163 AC XY: 663 AN XY: 4072

African (AFR) AF: 0.583 AC: 63 AN: 108

American (AMR) AF: 0.152 AC: 252 AN: 1656

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 11 AN: 94

East Asian (EAS) AF: 0.0515 AC: 31 AN: 602

South Asian (SAS) AF: 0.239 AC: 219 AN: 916

European-Finnish (FIN) AF: 0.117 AC: 14 AN: 120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.146 AC: 591 AN: 4036

Other (OTH) AF: 0.156 AC: 44 AN: 282

GnomAD4 genome AF: 0.318 AC: 48366 AN: 152186 Hom.: 11633 Cov.: 32 AF XY: 0.311 AC XY: 23182 AN XY: 74452

African (AFR) AF: 0.677 AC: 28062 AN: 41460

American (AMR) AF: 0.213 AC: 3252 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 770 AN: 3468

East Asian (EAS) AF: 0.0765 AC: 397 AN: 5192

South Asian (SAS) AF: 0.309 AC: 1492 AN: 4826

European-Finnish (FIN) AF: 0.126 AC: 1335 AN: 10610

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12228 AN: 68014

Other (OTH) AF: 0.272 AC: 575 AN: 2116

Alfa AF: 0.216 Hom.: 8730

Bravo AF: 0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.086
DANN	Benign	0.43
PhyloP100		-1.5
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: rs131842; hg19: chr22-37335773;