rs16997517

Variant names:

• chr22-36937894-C-G
• NM_000395.3:c.2086C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-36937894-C-G
• chr22-36937894-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000395.3(CSF2RB):​c.2086C>G​(p.Pro696Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. P696S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CSF2RB NM_000395.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.742

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16642714).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.2086C>G	p.Pro696Ala	missense_variant	Exon 14 of 14	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.2086C>G	p.Pro696Ala	missense_variant	Exon 14 of 14	5	NM_000395.3	ENSP00000384053.3
CSF2RB	ENST00000406230.5	c.2104C>G	p.Pro702Ala	missense_variant	Exon 13 of 13	1		ENSP00000385271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.92
DANN	Benign	0.93
DEOGEN2	Pathogenic	0.80	D;T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Uncertain	-0.058	T
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.2	D;.;D
REVEL	Benign	0.22
Sift	Benign	0.10	T;.;T
Sift4G	Uncertain	0.022	D;D;D
Polyphen		0.99	D;.;D
Vest4		0.043
MutPred		0.36		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);.;
MVP		0.91
MPC		0.21
ClinPred		0.46	T
GERP RS		-1.1
Varity_R		0.034
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-37333936;