rs2075726

Positions:

• chr22-36914004-G-A
• chr22-36914004-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000395.3(CSF2RB):​c.-173+327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,722 control chromosomes in the GnomAD database, including 15,250 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 0.43 (15250 hom., cov: 29)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.-173+327G>A		intron_variant		ENST00000403662.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.-173+327G>A		intron_variant		5	NM_000395.3	P1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64703 AN: 151604 Hom.: 15247 Cov.: 29

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.427 AC: 64723 AN: 151722 Hom.: 15250 Cov.: 29 AF XY: 0.431 AC XY: 31966 AN XY: 74118

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.446

Alfa AF: 0.492 Hom.: 40386

Bravo AF: 0.415

Asia WGS AF: 0.509 AC: 1766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.41
DANN	Benign	0.84

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: rs2075726; hg19: chr22-37310046;