chr22-36922437-G-A

Position:

• chr22-36922437-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+154G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 151,980 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.022 (74 hom., cov: 33)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.09

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=-0.92).
• BP6: Variant 22-36922437-G-A is Benign according to our data. Variant chr22-36922437-G-A is described in ClinVar as [Benign]. Clinvar id is 1183637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.76+154G>A		intron_variant		ENST00000403662.8
LOC105373023	XR_938230.2	n.194+3313C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.76+154G>A		intron_variant		5	NM_000395.3	P1
CSF2RB	ENST00000406230.5	c.76+154G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3361 AN: 151864 Hom.: 75 Cov.: 33

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00726

Gnomad FIN AF: 0.000945

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.00799

Gnomad OTH AF: 0.0279

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

GnomAD4 genome AF: 0.0221 AC: 3364 AN: 151980 Hom.: 74 Cov.: 33 AF XY: 0.0215 AC XY: 1597 AN XY: 74286

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.0186

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00727

Gnomad4 FIN AF: 0.000945

Gnomad4 NFE AF: 0.00800

Gnomad4 OTH AF: 0.0276

Alfa AF: 0.00251 Hom.: 1

Bravo AF: 0.0252

Asia WGS AF: 0.00895 AC: 32 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	Mar 24, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.74
DANN	Benign	0.51

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: rs116536124; hg19: chr22-37318479;