NM_000395.3:c.-172-164C>T

Variant names:

• chr22-36921872-C-T
• rs41280007
• NM_000395.3:c.-172-164C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000395.3(CSF2RB):​c.-172-164C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 152,300 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.054 (242 hom., cov: 33)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.538
• 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: DEFINITIVE, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000304449 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-36921872-C-T is Benign according to our data. Variant chr22-36921872-C-T is described in ClinVar as Benign. ClinVar VariationId is 1178164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0945 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.-172-164C>T		intron	N/A	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.-172-164C>T		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.-172-164C>T		intron	N/A	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000910856.1		c.-172-164C>T		intron	N/A	ENSP00000580915.1
	CSF2RB	ENST00000910857.1		c.-172-164C>T		intron	N/A	ENSP00000580916.1

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8179 AN: 152182 Hom.: 241 Cov.: 33

Gnomad AFR AF: 0.0690

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0400

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.0569

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

GnomAD4 genome AF: 0.0537 AC: 8186 AN: 152300 Hom.: 242 Cov.: 33 AF XY: 0.0541 AC XY: 4026 AN XY: 74466

African (AFR) AF: 0.0689 AC: 2862 AN: 41542

American (AMR) AF: 0.0399 AC: 611 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3472

East Asian (EAS) AF: 0.0419 AC: 217 AN: 5178

South Asian (SAS) AF: 0.102 AC: 492 AN: 4828

European-Finnish (FIN) AF: 0.0518 AC: 550 AN: 10626

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0465 AC: 3162 AN: 68026

Other (OTH) AF: 0.0572 AC: 121 AN: 2114

Alfa AF: 0.0530 Hom.: 87

Bravo AF: 0.0524

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		-0.54
PromoterAI		0.030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41280007; hg19: chr22-37317914;