Variant 17-40016855-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_172219.3(CSF3):c.511G>A(p.Ala171Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000932 in 1,613,460 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 2 hom. )

Consequence

CSF3
NM_172219.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.132

Variant links:

Genes affected

CSF3 (HGNC:2438): (colony stimulating factor 3) This gene encodes a member of the IL-6 superfamily of cytokines. The encoded cytokine controls the production, differentiation, and function of granulocytes. Granulocytes are a type of white blood cell that are part of the innate immune response. A modified form of this protein is commonly administered to manage chemotherapy-induced neutropenia. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2020]

CSF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004101336).

BP6

Variant 17-40016855-G-A is Benign according to our data. Variant chr17-40016855-G-A is described in ClinVar as [Benign]. Clinvar id is 720537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00513 (782/152316) while in subpopulation AFR AF= 0.0183 (760/41564). AF 95% confidence interval is 0.0172. There are 9 homozygotes in gnomad4. There are 377 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF3	NM_172219.3 linkuse as main transcript	c.511G>A	p.Ala171Thr	missense_variant	5/5	ENST00000394149.8	NP_757373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF3	ENST00000394149.8 linkuse as main transcript	c.511G>A	p.Ala171Thr	missense_variant	5/5	1	NM_172219.3	ENSP00000377705	A2	P09919-2

Frequencies

GnomAD3 genomes

AF:

0.00514

AC:

783

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

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:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00140

AC:

352

AN:

251142

Hom.:

AF XY:

0.00109

AC XY:

148

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0199

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000494

AC:

722

AN:

1461144

Hom.:

Cov.:

AF XY:

0.000410

AC XY:

298

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.000879

GnomAD4 genome

AF:

0.00513

AC:

782

AN:

152316

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0183

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000774

Hom.:

Bravo

AF:

0.00606

ESP6500AA

AF:

0.0168

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00180

AC:

218

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.38

DANN

Benign

0.77

DEOGEN2

Benign

0.19

.;.;T;.;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.52

T;T;T;T;T;T

MetaRNN

Benign

0.0041

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

.;.;N;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

1.3

.;N;N;N;N;.

REVEL

Benign

0.029

Sift

Benign

1.0

.;T;T;T;T;.

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

.;.;B;B;.;.

Vest4

0.017, 0.018, 0.016, 0.044, 0.026

MVP

0.29

MPC

0.31

ClinPred

0.0071

GERP RS

-2.6

Varity_R

0.085

gMVP

0.067

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