22-36927946-C-T

Position:

• chr22-36927946-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.392-1456C>T		intron_variant		ENST00000403662.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.392-1456C>T		intron_variant		5	NM_000395.3	P1
CSF2RB	ENST00000406230.5	c.392-1456C>T		intron_variant		1
CSF2RB	ENST00000421539.1	c.152-1456C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.389

Alfa AF: 0.429 Hom.: 21786

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

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

LitVar

Other links and lift over

dbSNP: rs909486; hg19: chr22-37323988; COSMIC: COSV53260627;