22-36921972-G-T

Position:

• chr22-36921972-G-T

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.-172-64G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 591,026 control chromosomes in the GnomAD database, including 76,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16648 hom., cov: 33)
  • Exomes 𝑓: 0.51 (59561 hom.)
• Consequence: CSF2RB NM_000395.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.04

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=-0.91).
• BP6: Variant 22-36921972-G-T is Benign according to our data. Variant chr22-36921972-G-T is described in ClinVar as [Benign]. Clinvar id is 1238097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.-172-64G>T		intron_variant		ENST00000403662.8
LOC105373023	XR_938230.2	n.195-3033C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.-172-64G>T		intron_variant		5	NM_000395.3	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66742 AN: 151988 Hom.: 16639 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.513 AC: 225329 AN: 438920 Hom.: 59561 AF XY: 0.508 AC XY: 116864 AN XY: 230054

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.626

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.611

Gnomad4 SAS exome AF: 0.406

Gnomad4 FIN exome AF: 0.573

Gnomad4 NFE exome AF: 0.522

Gnomad4 OTH exome AF: 0.505

GnomAD4 genome AF: 0.439 AC: 66776 AN: 152106 Hom.: 16648 Cov.: 33 AF XY: 0.445 AC XY: 33110 AN XY: 74350

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.450

Alfa AF: 0.448 Hom.: 4042

Bravo AF: 0.430

Asia WGS AF: 0.492 AC: 1708 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	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.055
DANN	Benign	0.46

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: rs10222238; hg19: chr22-37318014;