Genetic Variant CSF2RA:c.-46A>G (chrX-1282541-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001161529.2(CSF2RA):c.-46A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 747,374 control chromosomes in the GnomAD database, including 4,617 homozygotes. There are 39,899 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 752 hom., 6459 hem., cov: 31)

Exomes 𝑓: 0.11 ( 3865 hom. 33440 hem. )

Consequence

CSF2RA
NM_001161529.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0180

Variant links:

Genes affected

CSF2RA (HGNC:2435): (colony stimulating factor 2 receptor subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric receptor for colony stimulating factor 2, a cytokine which controls the production, differentiation, and function of granulocytes and macrophages. The encoded protein is a member of the cytokine family of receptors. This gene is found in the pseudoautosomal region (PAR) of the X and Y chromosomes. Multiple transcript variants encoding different isoforms have been found for this gene, with some of the isoforms being membrane-bound and others being soluble. [provided by RefSeq, Jul 2008]

CSF2RA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-1282541-A-G is Benign according to our data. Variant chrX-1282541-A-G is described in ClinVar as [Benign]. Clinvar id is 1265683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RA	NM_172245.4 link	c.-26-137A>G		intron_variant	Intron 2 of 12	ENST00000381529.9	NP_758448.1	P15509-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF2RA	ENST00000381529.9 link	c.-26-137A>G		intron_variant	Intron 2 of 12	1	NM_172245.4	ENSP00000370940.3		P15509-1

Frequencies

GnomAD3 genomes

AF:

0.0850

AC:

12908

AN:

151894

Hom.:

753

Cov.:

AF XY:

0.0871

AC XY:

6458

AN XY:

74142

show subpopulations

Gnomad AFR

AF:

0.0223

Gnomad AMI

AF:

0.0529

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.0720

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.0738

Gnomad FIN

AF:

0.159

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.0722

GnomAD4 exome

AF:

0.107

AC:

63434

AN:

595362

Hom.:

3865

Cov.:

AF XY:

0.104

AC XY:

33440

AN XY:

321414

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.0714

Gnomad4 EAS exome

AF:

0.0409

Gnomad4 SAS exome

AF:

0.0792

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.0949

GnomAD4 genome

AF:

0.0849

AC:

12903

AN:

152012

Hom.:

752

Cov.:

AF XY:

0.0870

AC XY:

6459

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.0720

Gnomad4 EAS

AF:

0.0251

Gnomad4 SAS

AF:

0.0747

Gnomad4 FIN

AF:

0.159

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.0715

Bravo

AF:

0.0812

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 31, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.1

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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