rs3795523

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016343.4(CENPF):c.2260C>G(p.Gln754Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 1,613,914 control chromosomes in the GnomAD database, including 4,160 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 0.072 ( 465 hom., cov: 33)

Exomes 𝑓: 0.062 ( 3695 hom. )

Consequence

CENPF
NM_016343.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.91

Publications

23 publications found

Variant links:

Genes affected

CENPF (HGNC:1857): (centromere protein F) This gene encodes a protein that associates with the centromere-kinetochore complex. The protein is a component of the nuclear matrix during the G2 phase of interphase. In late G2 the protein associates with the kinetochore and maintains this association through early anaphase. It localizes to the spindle midzone and the intracellular bridge in late anaphase and telophase, respectively, and is thought to be subsequently degraded. The localization of this protein suggests that it may play a role in chromosome segregation during mitotis. It is thought to form either a homodimer or heterodimer. Autoantibodies against this protein have been found in patients with cancer or graft versus host disease. [provided by RefSeq, Jul 2008]

CENPF Gene-Disease associations (from GenCC):

Stromme syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Illumina, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

CENPF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015101135).

BP6

Variant 1-214640598-C-G is Benign according to our data. Variant chr1-214640598-C-G is described in ClinVar as [Benign]. Clinvar id is 1209811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPF	NM_016343.4 link	c.2260C>G	p.Gln754Glu	missense_variant	Exon 12 of 20	ENST00000366955.8	NP_057427.3	P49454
CENPF	XM_017000086.3 link	c.2260C>G	p.Gln754Glu	missense_variant	Exon 12 of 20		XP_016855575.1	P49454
CENPF	XM_011509082.4 link	c.2260C>G	p.Gln754Glu	missense_variant	Exon 12 of 19		XP_011507384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8 link	c.2260C>G	p.Gln754Glu	missense_variant	Exon 12 of 20	1	NM_016343.4	ENSP00000355922.3		P49454
CENPF	ENST00000706765.1 link	c.2260C>G	p.Gln754Glu	missense_variant	Exon 12 of 19			ENSP00000516538.1		A0A9L9PXU7

Frequencies

GnomAD3 genomes

AF:

0.0714

AC:

10863

AN:

152090

Hom.:

463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0951

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.0217

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0499

Gnomad OTH

AF:

0.0689

GnomAD2 exomes

AF:

0.0831

AC:

20822

AN:

250658

AF XY:

0.0817

show subpopulations

Gnomad AFR exome

AF:

0.0981

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.0541

Gnomad EAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.0252

Gnomad NFE exome

AF:

0.0488

Gnomad OTH exome

AF:

0.0652

GnomAD4 exome

AF:

0.0621

AC:

90707

AN:

1461706

Hom.:

3695

Cov.:

AF XY:

0.0638

AC XY:

46404

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.0976

AC:

3268

AN:

33476

American (AMR)

AF:

0.148

AC:

6602

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0517

AC:

1351

AN:

26126

East Asian (EAS)

AF:

0.124

AC:

4917

AN:

39694

South Asian (SAS)

AF:

0.145

AC:

12542

AN:

86244

European-Finnish (FIN)

AF:

0.0268

AC:

1429

AN:

53406

Middle Eastern (MID)

AF:

0.0709

AC:

409

AN:

5766

European-Non Finnish (NFE)

AF:

0.0505

AC:

56190

AN:

1111900

Other (OTH)

AF:

0.0662

AC:

3999

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

5061

10122

15182

20243

25304

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0716

AC:

10896

AN:

152208

Hom.:

465

Cov.:

AF XY:

0.0724

AC XY:

5388

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0954

AC:

3962

AN:

41524

American (AMR)

AF:

0.107

AC:

1631

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0521

AC:

181

AN:

3472

East Asian (EAS)

AF:

0.119

AC:

619

AN:

5180

South Asian (SAS)

AF:

0.140

AC:

675

AN:

4818

European-Finnish (FIN)

AF:

0.0217

AC:

230

AN:

10602

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0500

AC:

3397

AN:

68006

Other (OTH)

AF:

0.0701

AC:

148

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

512

1024

1535

2047

2559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0508

Hom.:

198

Bravo

AF:

0.0799

TwinsUK

AF:

0.0574

AC:

213

ALSPAC

AF:

0.0501

AC:

193

ESP6500AA

AF:

0.0908

AC:

400

ESP6500EA

AF:

0.0541

AC:

465

ExAC

AF:

0.0819

AC:

9946

Asia WGS

AF:

0.122

AC:

423

AN:

3478

EpiCase

AF:

0.0505

EpiControl

AF:

0.0519

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Stromme syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.018

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.90

PhyloP100

1.9

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.69

REVEL

Benign

0.026

Sift

Benign

0.21

Sift4G

Benign

0.66

Polyphen

0.16

Vest4

0.089

MPC

0.083

ClinPred

0.0032

GERP RS

3.8

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.076

gMVP

0.043

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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rs3795523

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over