NM_000395.3:c.392-1456C>T

Variant names:

• chr22-36927946-C-T
• rs909486
• NM_000395.3:c.392-1456C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000395.3(CSF2RB):​c.392-1456C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,046 control chromosomes in the GnomAD database, including 13,775 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (13775 hom., cov: 32)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 20 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RB	NM_000395.3	c.392-1456C>T		intron_variant	Intron 4 of 13	ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8	c.392-1456C>T		intron_variant	Intron 4 of 13	5	NM_000395.3	ENSP00000384053.3
CSF2RB	ENST00000406230.5	c.392-1456C>T		intron_variant	Intron 3 of 12	1		ENSP00000385271.1
CSF2RB	ENST00000421539.1	c.152-1456C>T		intron_variant	Intron 3 of 6	5		ENSP00000393585.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58485 AN: 151928 Hom.: 13769 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.385 AC: 58502 AN: 152046 Hom.: 13775 Cov.: 32 AF XY: 0.397 AC XY: 29483 AN XY: 74318

African (AFR) AF: 0.123 AC: 5094 AN: 41480

American (AMR) AF: 0.535 AC: 8179 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1346 AN: 3468

East Asian (EAS) AF: 0.777 AC: 4004 AN: 5154

South Asian (SAS) AF: 0.432 AC: 2081 AN: 4820

European-Finnish (FIN) AF: 0.578 AC: 6109 AN: 10564

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30468 AN: 67966

Other (OTH) AF: 0.389 AC: 823 AN: 2114

Alfa AF: 0.426 Hom.: 54100

Bravo AF: 0.374

Asia WGS AF: 0.590 AC: 2051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.49
PhyloP100		-0.21
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: rs909486; hg19: chr22-37323988; COSMIC: COSV53260627;