1-214641961-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016343.4(CENPF):c.3623C>T(p.Ala1208Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00896 in 1,599,682 control chromosomes in the GnomAD database, including 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 22 hom., cov: 33)

Exomes 𝑓: 0.0089 ( 138 hom. )

Consequence

CENPF
NM_016343.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.61

Publications

9 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=0.0026867688).

BP6

Variant 1-214641961-C-T is Benign according to our data. Variant chr1-214641961-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00978 (1488/152162) while in subpopulation NFE AF = 0.00941 (640/67998). AF 95% confidence interval is 0.00881. There are 22 homozygotes in GnomAd4. There are 859 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPF	NM_016343.4 link	c.3623C>T	p.Ala1208Val	missense_variant	Exon 12 of 20	ENST00000366955.8	NP_057427.3	P49454
CENPF	XM_017000086.3 link	c.3623C>T	p.Ala1208Val	missense_variant	Exon 12 of 20		XP_016855575.1	P49454
CENPF	XM_011509082.4 link	c.3623C>T	p.Ala1208Val	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.3623C>T	p.Ala1208Val	missense_variant	Exon 12 of 20	1	NM_016343.4	ENSP00000355922.3		P49454
CENPF	ENST00000706765.1 link	c.3623C>T	p.Ala1208Val	missense_variant	Exon 12 of 19			ENSP00000516538.1		A0A9L9PXU7

Frequencies

GnomAD3 genomes

AF:

0.00979

AC:

1488

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.0579

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00941

Gnomad OTH

AF:

0.00863

GnomAD2 exomes

AF:

0.0118

AC:

2774

AN:

234930

AF XY:

0.0119

show subpopulations

Gnomad AFR exome

AF:

0.00139

Gnomad AMR exome

AF:

0.00499

Gnomad ASJ exome

AF:

0.00432

Gnomad EAS exome

AF:

0.0000567

Gnomad FIN exome

AF:

0.0589

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.0146

GnomAD4 exome

AF:

0.00888

AC:

12850

AN:

1447520

Hom.:

138

Cov.:

AF XY:

0.00883

AC XY:

6356

AN XY:

719614

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

32382

American (AMR)

AF:

0.00528

AC:

217

AN:

41098

Ashkenazi Jewish (ASJ)

AF:

0.00395

AC:

100

AN:

25300

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39628

South Asian (SAS)

AF:

0.00513

AC:

424

AN:

82726

European-Finnish (FIN)

AF:

0.0547

AC:

2897

AN:

52976

Middle Eastern (MID)

AF:

0.0264

AC:

150

AN:

5678

European-Non Finnish (NFE)

AF:

0.00768

AC:

8506

AN:

1108058

Other (OTH)

AF:

0.00845

AC:

504

AN:

59674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

625

1250

1876

2501

3126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00978

AC:

1488

AN:

152162

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

859

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41506

American (AMR)

AF:

0.00765

AC:

117

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00456

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0579

AC:

612

AN:

10574

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00941

AC:

640

AN:

67998

Other (OTH)

AF:

0.00854

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

151

227

302

378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00812

Hom.:

Bravo

AF:

0.00529

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00780

AC:

ExAC

AF:

0.0110

AC:

1339

Asia WGS

AF:

0.00144

AC:

AN:

3476

EpiCase

AF:

0.00792

EpiControl

AF:

0.00866

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CENPF: BP4, BS2 -

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

May 24, 2017

Genetic Services Laboratory, University of Chicago

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

0.12

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.018

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.0

PhyloP100

1.6

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.70

Vest4

0.028

MPC

0.053

ClinPred

0.0072

GERP RS

2.4

Varity_R

0.015

gMVP

0.051

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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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