rs117937233

Variant names:

• chr22-36922133-C-A
• rs117937233
• NM_000395.3:c.-75C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-36922133-C-A
• chr22-36922133-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000395.3(CSF2RB):​c.-75C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000082 in 1,219,548 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: CSF2RB NM_000395.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.-75C>A		5_prime_UTR_variant	Exon 2 of 14	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.-75C>A		5_prime_UTR_variant	Exon 2 of 14	5	NM_000395.3	ENSP00000384053.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.20e-7 AC: 1 AN: 1219548 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 608338

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28176

American (AMR) AF: 0.00 AC: 0 AN: 35410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24124

East Asian (EAS) AF: 0.00 AC: 0 AN: 34858

South Asian (SAS) AF: 0.00 AC: 0 AN: 75686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3792

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 924070

Other (OTH) AF: 0.00 AC: 0 AN: 51958

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.37
PhyloP100		0.62
PromoterAI		0.031	Neutral

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: rs117937233; hg19: chr22-37318175;