Genetic Variant ENST00000432318:c.-102G>A (chrX-1282485-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The ENST00000432318(CSF2RA):c.-102G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 635,396 control chromosomes in the GnomAD database, including 547 homozygotes. There are 4,022 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 418 hom., 2879 hem., cov: 31)

Exomes 𝑓: 0.0053 ( 129 hom. 1143 hem. )

Consequence

CSF2RA
ENST00000432318 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.42

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=-0.56).

BP6

Variant X-1282485-G-A is Benign according to our data. Variant chrX-1282485-G-A is described in ClinVar as [Benign]. Clinvar id is 1268410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF2RA	NM_172245.4 link	c.-26-193G>A		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.-26-193G>A		intron_variant	Intron 2 of 12	1	NM_172245.4	ENSP00000370940.3		P15509-1

Frequencies

GnomAD3 genomes

AF:

0.0407

AC:

6187

AN:

151908

Hom.:

418

Cov.:

AF XY:

0.0387

AC XY:

2870

AN XY:

74160

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.0283

GnomAD4 exome

AF:

0.00526

AC:

2541

AN:

483370

Hom.:

129

Cov.:

AF XY:

0.00445

AC XY:

1143

AN XY:

257032

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.00790

Gnomad4 ASJ exome

AF:

0.000471

Gnomad4 EAS exome

AF:

0.00127

Gnomad4 SAS exome

AF:

0.00138

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000504

Gnomad4 OTH exome

AF:

0.00937

GnomAD4 genome

AF:

0.0407

AC:

6193

AN:

152026

Hom.:

418

Cov.:

AF XY:

0.0388

AC XY:

2879

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.0141

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.0280

Bravo

AF:

0.0458

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

- -

Sep 24, 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

-0.56

CADD

Benign

0.080

DANN

Benign

0.86

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

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