Variant 5-132074935-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000758.4(CSF2):c.327G>A(p.Pro109Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,613,462 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00065 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

CSF2
NM_000758.4 splice_region, synonymous

Scores

Splicing: ADA: 0.4022

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.139

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 5-132074935-G-A is Benign according to our data. Variant chr5-132074935-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 787041.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.139 with no splicing effect.

BS2

High AC in GnomAd4 at 99 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2	NM_000758.4 linkuse as main transcript	c.327G>A	p.Pro109Pro	splice_region_variant, synonymous_variant	3/4	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.327G>A	p.Pro109Pro	splice_region_variant, synonymous_variant	3/4	1	NM_000758.4	ENSP00000296871.2		P04141

Frequencies

GnomAD3 genomes

AF:

0.000637

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000191

AC:

AN:

250892

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00236

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000712

AC:

104

AN:

1461152

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000650

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000150

Hom.:

Bravo

AF:

0.000718

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.40

dbscSNV1_RF

Benign

0.55

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