rs1801117

Variant names:

• chr22-36933957-C-T
• rs1801117
• NM_000395.3:c.1278C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36933957-C-T
• chr22-36933957-C-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000395.3(CSF2RB):​c.1278C>T​(p.Ser426Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,612,486 control chromosomes in the GnomAD database, including 39,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3444 hom., cov: 31)
  • Exomes 𝑓: 0.22 (36338 hom.)
• Consequence: CSF2RB NM_000395.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.990
• Publications: 16 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 22-36933957-C-T is Benign according to our data. Variant chr22-36933957-C-T is described in ClinVar as Benign. ClinVar VariationId is 226545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 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.1278C>T	p.Ser426Ser	synonymous	Exon 10 of 14	NP_000386.1	P32927-1
	CSF2RB	NM_001410827.1		c.1296C>T	p.Ser432Ser	synonymous	Exon 10 of 14	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.1278C>T	p.Ser426Ser	synonymous	Exon 10 of 14	ENSP00000384053.3	P32927-1
	CSF2RB	ENST00000406230.5	TSL:1	c.1296C>T	p.Ser432Ser	synonymous	Exon 9 of 13	ENSP00000385271.1	P32927-2
	CSF2RB	ENST00000910856.1		c.1278C>T	p.Ser426Ser	synonymous	Exon 10 of 14	ENSP00000580915.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31404 AN: 151816 Hom.: 3444 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.218

GnomAD2 exomes AF: 0.189 AC: 47091 AN: 249068 AF XY: 0.195

Gnomad AFR exome AF: 0.238

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.0615

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.218 AC: 318672 AN: 1460552 Hom.: 36338 Cov.: 38 AF XY: 0.219 AC XY: 159139 AN XY: 726608

African (AFR) AF: 0.235 AC: 7882 AN: 33480

American (AMR) AF: 0.113 AC: 5070 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4984 AN: 26136

East Asian (EAS) AF: 0.0488 AC: 1939 AN: 39696

South Asian (SAS) AF: 0.236 AC: 20335 AN: 86248

European-Finnish (FIN) AF: 0.151 AC: 7876 AN: 52184

Middle Eastern (MID) AF: 0.238 AC: 1375 AN: 5768

European-Non Finnish (NFE) AF: 0.230 AC: 255714 AN: 1111940

Other (OTH) AF: 0.224 AC: 13497 AN: 60384

GnomAD4 genome AF: 0.207 AC: 31407 AN: 151934 Hom.: 3444 Cov.: 31 AF XY: 0.199 AC XY: 14796 AN XY: 74268

African (AFR) AF: 0.235 AC: 9735 AN: 41432

American (AMR) AF: 0.151 AC: 2309 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3462

East Asian (EAS) AF: 0.0671 AC: 347 AN: 5172

South Asian (SAS) AF: 0.208 AC: 1000 AN: 4816

European-Finnish (FIN) AF: 0.138 AC: 1455 AN: 10560

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.224 AC: 15194 AN: 67900

Other (OTH) AF: 0.215 AC: 454 AN: 2112

Alfa AF: 0.217 Hom.: 7019

Bravo AF: 0.209

Asia WGS AF: 0.125 AC: 439 AN: 3478

EpiCase AF: 0.227

EpiControl AF: 0.227

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.5
DANN	Benign	0.49
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.26		Position offset: 37

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1801117; hg19: chr22-37329999; COSMIC: COSV53256458; COSMIC: COSV53256458;