chr22-36938208-G-A

Variant names:

• chr22-36938208-G-A
• rs1801116
• NM_000395.3:c.2400G>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_001410827.1(CSF2RB):​c.2418G>A​(p.Pro806Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,614,078 control chromosomes in the GnomAD database, including 710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (44 hom., cov: 32)
  • Exomes 𝑓: 0.028 (666 hom.)
• Consequence: CSF2RB NM_001410827.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.287
• Publications: 6 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=-0.8).
• BP6: Variant 22-36938208-G-A is Benign according to our data. Variant chr22-36938208-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.287 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0231 (3514/152224) while in subpopulation NFE AF = 0.0282 (1917/67990). AF 95% confidence interval is 0.0271. There are 44 homozygotes in GnomAd4. There are 1683 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001410827.1. 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.2400G>A	p.Pro800Pro	synonymous	Exon 14 of 14	NP_000386.1
	CSF2RB	NM_001410827.1		c.2418G>A	p.Pro806Pro	synonymous	Exon 14 of 14	NP_001397756.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RB	ENST00000403662.8	TSL:5 MANE Select	c.2400G>A	p.Pro800Pro	synonymous	Exon 14 of 14	ENSP00000384053.3
	CSF2RB	ENST00000406230.5	TSL:1	c.2418G>A	p.Pro806Pro	synonymous	Exon 13 of 13	ENSP00000385271.1
	CSF2RB	ENST00000910856.1		c.2436G>A	p.Pro812Pro	synonymous	Exon 14 of 14	ENSP00000580915.1

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3512 AN: 152106 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0245

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0282

Gnomad OTH AF: 0.0263

GnomAD2 exomes AF: 0.0229 AC: 5758 AN: 251372 AF XY: 0.0236

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.0309

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0272

Gnomad NFE exome AF: 0.0294

Gnomad OTH exome AF: 0.0299

GnomAD4 exome AF: 0.0284 AC: 41549 AN: 1461854 Hom.: 666 Cov.: 35 AF XY: 0.0284 AC XY: 20685 AN XY: 727226

African (AFR) AF: 0.0162 AC: 544 AN: 33480

American (AMR) AF: 0.0111 AC: 498 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 869 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0230 AC: 1981 AN: 86258

European-Finnish (FIN) AF: 0.0280 AC: 1494 AN: 53402

Middle Eastern (MID) AF: 0.0499 AC: 288 AN: 5766

European-Non Finnish (NFE) AF: 0.0308 AC: 34305 AN: 1111996

Other (OTH) AF: 0.0260 AC: 1569 AN: 60392

GnomAD4 genome AF: 0.0231 AC: 3514 AN: 152224 Hom.: 44 Cov.: 32 AF XY: 0.0226 AC XY: 1683 AN XY: 74422

African (AFR) AF: 0.0164 AC: 681 AN: 41538

American (AMR) AF: 0.0202 AC: 309 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.0232 AC: 112 AN: 4822

European-Finnish (FIN) AF: 0.0245 AC: 260 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0282 AC: 1917 AN: 67990

Other (OTH) AF: 0.0260 AC: 55 AN: 2112

Alfa AF: 0.0275 Hom.: 31

Bravo AF: 0.0220

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0293

EpiControl AF: 0.0291

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	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.5
DANN	Benign	0.40
PhyloP100		0.29
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: rs1801116; hg19: chr22-37334250;