22-36921806-T-C

Variant names:

• chr22-36921806-T-C
• rs5756408
• NM_000395.3:c.-172-230T>C

Variant summary

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

The NM_000395.3(CSF2RB):​c.-172-230T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,746 control chromosomes in the GnomAD database, including 16,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (16889 hom., cov: 32)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.03
• Publications: 2 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: DEFINITIVE, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000304449 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 22-36921806-T-C is Benign according to our data. Variant chr22-36921806-T-C is described in ClinVar as Benign. ClinVar VariationId is 1271192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000395.3. 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.-172-230T>C		intron	N/A	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.-172-230T>C		intron	N/A	NP_001397756.1	P32927-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.-172-230T>C		intron	N/A	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000910856.1		c.-172-230T>C		intron	N/A	ENSP00000580915.1
	CSF2RB	ENST00000910857.1		c.-172-230T>C		intron	N/A	ENSP00000580916.1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67182 AN: 151630 Hom.: 16881 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.443 AC: 67215 AN: 151746 Hom.: 16889 Cov.: 32 AF XY: 0.450 AC XY: 33363 AN XY: 74164

African (AFR) AF: 0.198 AC: 8172 AN: 41188

American (AMR) AF: 0.590 AC: 9025 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3468

East Asian (EAS) AF: 0.599 AC: 3091 AN: 5158

South Asian (SAS) AF: 0.398 AC: 1918 AN: 4824

European-Finnish (FIN) AF: 0.563 AC: 5962 AN: 10582

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35684 AN: 67924

Other (OTH) AF: 0.452 AC: 952 AN: 2108

Alfa AF: 0.331 Hom.: 1135

Bravo AF: 0.434

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	-0.96
CADD	Benign	0.81
DANN	Benign	0.22
PhyloP100		-4.0
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs5756408; hg19: chr22-37317848;