22-36922404-G-A

Position:

• chr22-36922404-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000395.3(CSF2RB):​c.76+121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 899,718 control chromosomes in the GnomAD database, including 116,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16529 hom., cov: 32)
  • Exomes 𝑓: 0.51 (100025 hom.)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.17

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-36922404-G-A is Benign according to our data. Variant chr22-36922404-G-A is described in ClinVar as [Benign]. Clinvar id is 1263392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.76+121G>A		intron_variant		ENST00000403662.8
LOC105373023	XR_938230.2	n.194+3346C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.76+121G>A		intron_variant		5	NM_000395.3	P1
CSF2RB	ENST00000406230.5	c.76+121G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66496 AN: 151630 Hom.: 16520 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.507 AC: 379281 AN: 747970 Hom.: 100025 AF XY: 0.504 AC XY: 194365 AN XY: 385840

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.502

Gnomad4 EAS exome AF: 0.608

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.568

Gnomad4 NFE exome AF: 0.513

Gnomad4 OTH exome AF: 0.495

GnomAD4 genome AF: 0.438 AC: 66530 AN: 151748 Hom.: 16529 Cov.: 32 AF XY: 0.444 AC XY: 32952 AN XY: 74134

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.448

Alfa AF: 0.481 Hom.: 2325

Bravo AF: 0.430

Asia WGS AF: 0.495 AC: 1721 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.027
DANN	Benign	0.37

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: rs2075940; hg19: chr22-37318446; COSMIC: COSV53261015; COSMIC: COSV53261015;