Variant rs117405606 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.197

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2RB	NM_000395.3 linkuse as main transcript	c.1153-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000403662.8	NP_000386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF2RB	ENST00000403662.8 linkuse as main transcript	c.1153-13T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_000395.3	ENSP00000384053	P1	P32927-1
CSF2RB	ENST00000406230.5 linkuse as main transcript	c.1171-13T>C		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000385271		P32927-2

Frequencies

GnomAD3 genomes

AF:

0.00844

AC:

1283

AN:

151996

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0117

AC XY:

1483

AN XY:

126704

show subpopulations

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.:

AF XY:

0.00765

AC XY:

5516

AN XY:

721492

show subpopulations

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.:

Cov.:

AF XY:

0.00904

AC XY:

672

AN XY:

74366

show subpopulations

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.:

Bravo

AF:

0.00802

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over