rs117405606

chr22-36933819-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000395.3(CSF2RB):c.1153-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00668 in 1,602,758 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (16 hom., cov: 31)
  • Exomes 𝑓: 0.0065 (163 hom.)
• Consequence: CSF2RB NM_000395.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.197

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-36933819-T-C is Benign according to our data. Variant chr22-36933819-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 226544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00846 (1287/152114) while in subpopulation SAS AF= 0.051 (245/4804). AF 95% confidence interval is 0.0458. There are 16 homozygotes in gnomad4. There are 672 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RB	NM_000395.3	c.1153-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000403662.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RB	ENST00000403662.8	c.1153-13T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_000395.3	P1
CSF2RB	ENST00000406230.5	c.1171-13T>C		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00844 AC: 1283 AN: 151996 Hom.: 16 Cov.: 31

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00483

Gnomad SAS AF: 0.0510

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.0101 AC: 2357 AN: 232220 Hom.: 47 AF XY: 0.0117 AC XY: 1483 AN XY: 126704

Gnomad AFR exome AF: 0.0172

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00685

Gnomad SAS exome AF: 0.0458

Gnomad FIN exome AF: 0.00317

Gnomad NFE exome AF: 0.00386

Gnomad OTH exome AF: 0.00884

GnomAD4 exome AF: 0.00649 AC: 9414 AN: 1450644 Hom.: 163 Cov.: 31 AF XY: 0.00765 AC XY: 5516 AN XY: 721492

Gnomad4 AFR exome AF: 0.0175

Gnomad4 AMR exome AF: 0.00326

Gnomad4 ASJ exome AF: 0.000154

Gnomad4 EAS exome AF: 0.00733

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.00339

Gnomad4 NFE exome AF: 0.00344

Gnomad4 OTH exome AF: 0.00740

GnomAD4 genome AF: 0.00846 AC: 1287 AN: 152114 Hom.: 16 Cov.: 31 AF XY: 0.00904 AC XY: 672 AN XY: 74366

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00484

Gnomad4 SAS AF: 0.0510

Gnomad4 FIN AF: 0.00415

Gnomad4 NFE AF: 0.00321

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00447 Hom.: 1

Bravo AF: 0.00802

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 30, 2020	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

1153-13T>C in intron 9 of CSF2RB: This variant is not expected to have clinical significance because it has been identified in 1.5% (66/4382) of African America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs117405606). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.78
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs117405606; hg19: chr22-37329861;