chr22-36921972-G-T

Variant names:

• chr22-36921972-G-T
• rs10222238
• NM_000395.3:c.-172-64G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

CSF2RB Gene-Disease associations (from GenCC):

• surfactant metabolism dysfunction, pulmonary, 5

  Inheritance: AR Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000304449 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000395.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	NM_000395.3	MANE Select	c.-172-64G>T		intron	N/A	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.-172-64G>T		intron	N/A	NP_001397756.1	P32927-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.-172-64G>T		intron	N/A	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000910856.1		c.-172-64G>T		intron	N/A	ENSP00000580915.1
	CSF2RB	ENST00000910857.1		c.-172-64G>T		intron	N/A	ENSP00000580916.1

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

African (AFR) AF: 0.190 AC: 2342 AN: 12310

American (AMR) AF: 0.626 AC: 11844 AN: 18934

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 6872 AN: 13512

East Asian (EAS) AF: 0.611 AC: 18739 AN: 30660

South Asian (SAS) AF: 0.406 AC: 18465 AN: 45496

European-Finnish (FIN) AF: 0.573 AC: 16665 AN: 29104

Middle Eastern (MID) AF: 0.485 AC: 936 AN: 1928

European-Non Finnish (NFE) AF: 0.522 AC: 136583 AN: 261474

Other (OTH) AF: 0.505 AC: 12883 AN: 25502

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

African (AFR) AF: 0.196 AC: 8146 AN: 41512

American (AMR) AF: 0.578 AC: 8842 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1771 AN: 3470

East Asian (EAS) AF: 0.575 AC: 2974 AN: 5170

South Asian (SAS) AF: 0.395 AC: 1908 AN: 4830

European-Finnish (FIN) AF: 0.563 AC: 5958 AN: 10578

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35603 AN: 67932

Other (OTH) AF: 0.450 AC: 952 AN: 2116

Alfa AF: 0.451 Hom.: 5428

Bravo AF: 0.430

Asia WGS AF: 0.492 AC: 1708 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.055
DANN	Benign	0.46
PhyloP100		-2.0
PromoterAI		-0.076	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10222238; hg19: chr22-37318014;