chr22-36922215-T-C

Variant names:

• chr22-36922215-T-C
• rs1363625718
• NM_000395.3:c.8T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000395.3(CSF2RB):​c.8T>C​(p.Leu3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,435,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L3Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CSF2RB NM_000395.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

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]

ENSG00000304449 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23492461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.8T>C	p.Leu3Pro	missense_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.8T>C	p.Leu3Pro	missense_variant	Exon 2 of 14	5	NM_000395.3	ENSP00000384053.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1435794 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 711710

African (AFR) AF: 0.00 AC: 0 AN: 33086

American (AMR) AF: 0.00 AC: 0 AN: 41474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25540

East Asian (EAS) AF: 0.00 AC: 0 AN: 38632

South Asian (SAS) AF: 0.00 AC: 0 AN: 82190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4426

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1099912

Other (OTH) AF: 0.00 AC: 0 AN: 59328

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	8.3
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T;T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.27	T;T;T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	1.4	L;.;L
PhyloP100		-0.20
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.4	N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	D;D;D
Sift4G	Benign	0.086	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.20
MutPred		0.48		Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MVP		0.87
MPC		0.30
ClinPred		0.21	T
GERP RS		-1.1
PromoterAI		0.026	Neutral
Varity_R		0.16
gMVP		0.64
Mutation Taster		=86/14	polymorphism

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

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Other links and lift over

dbSNP: rs1363625718; hg19: chr22-37318257;