Variant 5-132073889-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000758.4(CSF2):c.66G>A(p.Ser22Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,613,088 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 49 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 41 hom. )

Consequence

CSF2
NM_000758.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.25

Variant links:

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]

CSF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 5-132073889-G-A is Benign according to our data. Variant chr5-132073889-G-A is described in ClinVar as [Benign]. Clinvar id is 780564.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1967/152252) while in subpopulation AFR AF= 0.0437 (1815/41552). AF 95% confidence interval is 0.042. There are 49 homozygotes in gnomad4. There are 917 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1967 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2	NM_000758.4 linkuse as main transcript	c.66G>A	p.Ser22Ser	synonymous_variant	1/4	ENST00000296871.4	NP_000749.2	P04141

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF2	ENST00000296871.4 linkuse as main transcript	c.66G>A	p.Ser22Ser	synonymous_variant	1/4	1	NM_000758.4	ENSP00000296871.2		P04141

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1962

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0437

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00394

AC:

985

AN:

250224

Hom.:

AF XY:

0.00312

AC XY:

423

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.0439

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00157

AC:

2294

AN:

1460836

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1045

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.0417

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.0148

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.00368

GnomAD4 genome

AF:

0.0129

AC:

1967

AN:

152252

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

917

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0437

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00672

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.00260

AC:

AN:

3476

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.1

DANN

Benign

0.61

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