chr22-36938238-C-A

Variant names:

• chr22-36938238-C-A
• rs2228092
• NM_000395.3:c.2430C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000395.3(CSF2RB):​c.2430C>A​(p.Pro810Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00817 in 1,614,138 control chromosomes in the GnomAD database, including 267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P810P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.017 (57 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (210 hom.)
• Consequence: CSF2RB NM_000395.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.90
• 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: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 22-36938238-C-A is Benign according to our data. Variant chr22-36938238-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.9 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0168 (2562/152280) while in subpopulation SAS AF = 0.0491 (237/4822). AF 95% confidence interval is 0.0446. There are 57 homozygotes in GnomAd4. There are 1301 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 57 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	NM_000395.3	MANE Select	c.2430C>A	p.Pro810Pro	synonymous	Exon 14 of 14	NP_000386.1
	CSF2RB	NM_001410827.1		c.2448C>A	p.Pro816Pro	synonymous	Exon 14 of 14	NP_001397756.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.2430C>A	p.Pro810Pro	synonymous	Exon 14 of 14	ENSP00000384053.3
	CSF2RB	ENST00000406230.5	TSL:1	c.2448C>A	p.Pro816Pro	synonymous	Exon 13 of 13	ENSP00000385271.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2551 AN: 152162 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00306

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0120 AC: 3012 AN: 251388 AF XY: 0.0129

Gnomad AFR exome AF: 0.0460

Gnomad AMR exome AF: 0.00466

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00707

Gnomad FIN exome AF: 0.00564

Gnomad NFE exome AF: 0.00383

Gnomad OTH exome AF: 0.00913

GnomAD4 exome AF: 0.00727 AC: 10622 AN: 1461858 Hom.: 210 Cov.: 35 AF XY: 0.00830 AC XY: 6036 AN XY: 727228

African (AFR) AF: 0.0451 AC: 1509 AN: 33480

American (AMR) AF: 0.00478 AC: 214 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

East Asian (EAS) AF: 0.00723 AC: 287 AN: 39700

South Asian (SAS) AF: 0.0441 AC: 3802 AN: 86258

European-Finnish (FIN) AF: 0.00562 AC: 300 AN: 53404

Middle Eastern (MID) AF: 0.0114 AC: 66 AN: 5768

European-Non Finnish (NFE) AF: 0.00346 AC: 3851 AN: 1111994

Other (OTH) AF: 0.00975 AC: 589 AN: 60394

GnomAD4 genome AF: 0.0168 AC: 2562 AN: 152280 Hom.: 57 Cov.: 32 AF XY: 0.0175 AC XY: 1301 AN XY: 74470

African (AFR) AF: 0.0463 AC: 1924 AN: 41556

American (AMR) AF: 0.00510 AC: 78 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5180

South Asian (SAS) AF: 0.0491 AC: 237 AN: 4822

European-Finnish (FIN) AF: 0.00574 AC: 61 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00307 AC: 209 AN: 68000

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.00641 Hom.: 31

Bravo AF: 0.0167

Asia WGS AF: 0.0230 AC: 80 AN: 3478

EpiCase AF: 0.00316

EpiControl AF: 0.00427

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	CSF2RB-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.12
DANN	Benign	0.57
PhyloP100		-3.9
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: rs2228092; hg19: chr22-37334280;