X-1282897-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_172245.4(CSF2RA):c.76+118C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 921,878 control chromosomes in the GnomAD database, including 12 homozygotes. There are 1,098 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (7 hom., 401 hem., cov: 31)
  • Exomes 𝑓: 0.0018 (5 hom. 697 hem.)
• Consequence: CSF2RA NM_172245.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-1282897-C-G is Benign according to our data. Variant chrX-1282897-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1197538.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00526 (801/152194) while in subpopulation AFR AF= 0.0147 (610/41540). AF 95% confidence interval is 0.0137. There are 7 homozygotes in gnomad4. There are 401 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSF2RA	NM_172245.4	c.76+118C>G		intron_variant		ENST00000381529.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSF2RA	ENST00000381529.9	c.76+118C>G		intron_variant		1	NM_172245.4	A2

Frequencies

GnomAD3 genomes AF: 0.00525 AC: 798 AN: 152076 Hom.: 7 Cov.: 31 AF XY: 0.00536 AC XY: 398 AN XY: 74294

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000912

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.00181 AC: 1392 AN: 769684 Hom.: 5 AF XY: 0.00171 AC XY: 697 AN XY: 408612

Gnomad4 AFR exome AF: 0.0155

Gnomad4 AMR exome AF: 0.00481

Gnomad4 ASJ exome AF: 0.00909

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000592

Gnomad4 FIN exome AF: 0.0000941

Gnomad4 NFE exome AF: 0.000905

Gnomad4 OTH exome AF: 0.00421

GnomAD4 genome AF: 0.00526 AC: 801 AN: 152194 Hom.: 7 Cov.: 31 AF XY: 0.00539 AC XY: 401 AN XY: 74422

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.00426

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000912

Gnomad4 OTH AF: 0.00521

Bravo AF: 0.00608

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 21, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.0
Dann	Benign	0.76

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

Other links and lift over

dbSNP: rs143197304; hg19: chrX-1401790;