rs743564

Positions:

• chr5-132075186-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000296871.4(CSF2):​c.327+251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,190 control chromosomes in the GnomAD database, including 8,392 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (8392 hom., cov: 34)
• Consequence: CSF2 ENST00000296871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

Genes affected

CSF2 (HGNC:2434): (colony stimulating factor 2) The protein encoded by this gene is a cytokine that controls the production, differentiation, and function of granulocytes and macrophages. The active form of the protein is found extracellularly as a homodimer. This gene has been localized to a cluster of related genes at chromosome region 5q31, which is known to be associated with interstitial deletions in the 5q- syndrome and acute myelogenous leukemia. Other genes in the cluster include those encoding interleukins 4, 5, and 13. This gene plays a role in promoting tissue inflammation. Elevated levels of cytokines, including the one produced by this gene, have been detected in SARS-CoV-2 infected patients that develop acute respiratory distress syndrome. Mice deficient in this gene or its receptor develop pulmonary alveolar proteinosis. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2	NM_000758.4	c.327+251T>C		intron_variant		ENST00000296871.4	NP_000749.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF2	ENST00000296871.4	c.327+251T>C		intron_variant		1	NM_000758.4	ENSP00000296871	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48368 AN: 152072 Hom.: 8390 Cov.: 34

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.348

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.318 AC: 48387 AN: 152190 Hom.: 8392 Cov.: 34 AF XY: 0.304 AC XY: 22615 AN XY: 74422

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.343

Alfa AF: 0.362 Hom.: 2633

Bravo AF: 0.325

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs743564; hg19: chr5-131410879; COSMIC: COSV51522296; COSMIC: COSV51522296;