1-214640439-A-G

Variant names:

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.2101A>G(p.Met701Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 1,614,010 control chromosomes in the GnomAD database, including 4,158 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M701L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.072 ( 462 hom., cov: 33)

Exomes 𝑓: 0.062 ( 3696 hom. )

Consequence

CENPF
NM_016343.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.70

Publications

22 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=0.0017424524).

BP6

Variant 1-214640439-A-G is Benign according to our data. Variant chr1-214640439-A-G is described in ClinVar as [Benign]. Clinvar id is 1209810.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.2101A>G	p.Met701Val	missense_variant	Exon 12 of 20	ENST00000366955.8	NP_057427.3	P49454
CENPF	XM_017000086.3 link	c.2101A>G	p.Met701Val	missense_variant	Exon 12 of 20		XP_016855575.1	P49454
CENPF	XM_011509082.4 link	c.2101A>G	p.Met701Val	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.2101A>G	p.Met701Val	missense_variant	Exon 12 of 20	1	NM_016343.4	ENSP00000355922.3		P49454
CENPF	ENST00000706765.1 link	c.2101A>G	p.Met701Val	missense_variant	Exon 12 of 19			ENSP00000516538.1		A0A9L9PXU7

Frequencies

GnomAD3 genomes

AF:

0.0714

AC:

10861

AN:

152186

Hom.:

460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0951

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0522

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0500

Gnomad OTH

AF:

0.0688

GnomAD2 exomes

AF:

0.0831

AC:

20806

AN:

250402

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:

0.0650

GnomAD4 exome

AF:

0.0621

AC:

90704

AN:

1461706

Hom.:

3696

Cov.:

AF XY:

0.0638

AC XY:

46411

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.0976

AC:

3268

AN:

33476

American (AMR)

AF:

0.148

AC:

6605

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0517

AC:

1351

AN:

26130

East Asian (EAS)

AF:

0.124

AC:

4911

AN:

39684

South Asian (SAS)

AF:

0.145

AC:

12539

AN:

86234

European-Finnish (FIN)

AF:

0.0267

AC:

1428

AN:

53384

Middle Eastern (MID)

AF:

0.0711

AC:

410

AN:

5766

European-Non Finnish (NFE)

AF:

0.0505

AC:

56193

AN:

1111946

Other (OTH)

AF:

0.0662

AC:

3999

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

4928

9856

14783

19711

24639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0715

AC:

10894

AN:

152304

Hom.:

462

Cov.:

AF XY:

0.0724

AC XY:

5394

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0954

AC:

3963

AN:

41552

American (AMR)

AF:

0.107

AC:

1633

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0522

AC:

181

AN:

3470

East Asian (EAS)

AF:

0.118

AC:

611

AN:

5164

South Asian (SAS)

AF:

0.140

AC:

674

AN:

4822

European-Finnish (FIN)

AF:

0.0218

AC:

232

AN:

10626

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0500

AC:

3399

AN:

68038

Other (OTH)

AF:

0.0699

AC:

148

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

519

1038

1556

2075

2594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0611

Hom.:

950

Bravo

AF:

0.0803

TwinsUK

AF:

0.0574

AC:

213

ALSPAC

AF:

0.0501

AC:

193

ESP6500AA

AF:

0.0903

AC:

398

ESP6500EA

AF:

0.0542

AC:

466

ExAC

AF:

0.0819

AC:

9949

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

0.053

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.2

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.013

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.054

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.90

PhyloP100

1.7

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.29

REVEL

Benign

0.074

Sift

Benign

0.30

Sift4G

Benign

0.30

Polyphen

0.019

Vest4

0.0070

MPC

0.053

ClinPred

0.0030

GERP RS

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.064

Mutation Taster

=98/2

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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1-214640439-A-G

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