rs743564

Variant names:

• chr5-132075186-T-C
• rs743564
• NM_000758.4:c.327+251T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000758.4(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 NM_000758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000758.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2	NM_000758.4	MANE Select	c.327+251T>C		intron	N/A	NP_000749.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2	ENST00000296871.4	TSL:1 MANE Select	c.327+251T>C		intron	N/A	ENSP00000296871.2

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

African (AFR) AF: 0.276 AC: 11439 AN: 41454

American (AMR) AF: 0.308 AC: 4712 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1053 AN: 3472

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5188

South Asian (SAS) AF: 0.102 AC: 495 AN: 4832

European-Finnish (FIN) AF: 0.259 AC: 2750 AN: 10618

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26592 AN: 67996

Other (OTH) AF: 0.343 AC: 726 AN: 2116

Alfa AF: 0.371 Hom.: 4933

Bravo AF: 0.325

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.47
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs743564; hg19: chr5-131410879; COSMIC: COSV51522296; COSMIC: COSV51522296;