22-36921991-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000395.3(CSF2RB):c.-172-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 598,760 control chromosomes in the GnomAD database, including 598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (119 hom., cov: 33)
  • Exomes 𝑓: 0.041 (479 hom.)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

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]

LOC105373023 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-36921991-C-T is Benign according to our data. Variant chr22-36921991-C-T is described in ClinVar as [Benign]. Clinvar id is 1283425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0318 (4841/152292) while in subpopulation NFE AF= 0.0484 (3292/68008). AF 95% confidence interval is 0.047. There are 119 homozygotes in gnomad4. There are 2289 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 119 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.-172-45C>T		intron_variant		ENST00000403662.8
LOC105373023	XR_938230.2	n.195-3052G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.-172-45C>T		intron_variant		5	NM_000395.3	P1

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4844 AN: 152174 Hom.: 119 Cov.: 33

Gnomad AFR AF: 0.00874

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0413 AC: 18461 AN: 446468 Hom.: 479 Cov.: 3 AF XY: 0.0421 AC XY: 9868 AN XY: 234246

Gnomad4 AFR exome AF: 0.00800

Gnomad4 AMR exome AF: 0.0230

Gnomad4 ASJ exome AF: 0.0276

Gnomad4 EAS exome AF: 0.000130

Gnomad4 SAS exome AF: 0.0478

Gnomad4 FIN exome AF: 0.0348

Gnomad4 NFE exome AF: 0.0496

Gnomad4 OTH exome AF: 0.0392

GnomAD4 genome AF: 0.0318 AC: 4841 AN: 152292 Hom.: 119 Cov.: 33 AF XY: 0.0307 AC XY: 2289 AN XY: 74458

Gnomad4 AFR AF: 0.00871

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0404

Gnomad4 FIN AF: 0.0338

Gnomad4 NFE AF: 0.0484

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0464 Hom.: 26

Bravo AF: 0.0301

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.42
Dann	Benign	0.54

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: rs41280009; hg19: chr22-37318033;