rs11705394

Variant names:

• chr22-36933634-T-C
• rs11705394
• NM_000395.3:c.1153-198T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001410827.1(CSF2RB):​c.1171-198T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,096 control chromosomes in the GnomAD database, including 5,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5086 hom., cov: 32)
• Consequence: CSF2RB NM_001410827.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.534
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 22-36933634-T-C is Benign according to our data. Variant chr22-36933634-T-C is described in ClinVar as Benign. ClinVar VariationId is 1276886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001410827.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	NM_000395.3	MANE Select	c.1153-198T>C		intron	N/A	NP_000386.1
	CSF2RB	NM_001410827.1		c.1171-198T>C		intron	N/A	NP_001397756.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.1153-198T>C		intron	N/A	ENSP00000384053.3
	CSF2RB	ENST00000406230.5	TSL:1	c.1171-198T>C		intron	N/A	ENSP00000385271.1
	CSF2RB	ENST00000910856.1		c.1153-198T>C		intron	N/A	ENSP00000580915.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38076 AN: 151978 Hom.: 5087 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.250 AC: 38087 AN: 152096 Hom.: 5086 Cov.: 32 AF XY: 0.242 AC XY: 17978 AN XY: 74360

African (AFR) AF: 0.319 AC: 13214 AN: 41454

American (AMR) AF: 0.179 AC: 2744 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3466

East Asian (EAS) AF: 0.0680 AC: 352 AN: 5174

South Asian (SAS) AF: 0.235 AC: 1135 AN: 4822

European-Finnish (FIN) AF: 0.164 AC: 1735 AN: 10596

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17258 AN: 67972

Other (OTH) AF: 0.258 AC: 544 AN: 2112

Alfa AF: 0.253 Hom.: 7977

Bravo AF: 0.255

Asia WGS AF: 0.137 AC: 481 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.042
DANN	Benign	0.17
PhyloP100		-0.53
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: rs11705394; hg19: chr22-37329676;