rs131842

Positions:

• chr22-36939731-A-G
• chr22-36939731-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.*1229A>G		3_prime_UTR_variant	14/14	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.*1229A>G		3_prime_UTR_variant	14/14	5	NM_000395.3	ENSP00000384053	P1

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

Gnomad4 AFR exome AF: 0.583

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.0515

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.156

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

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0765

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.272

Alfa AF: 0.198 Hom.: 4876

Bravo AF: 0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.086
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs131842; hg19: chr22-37335773;