rs438034

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.8827A>G(p.Arg2943Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,613,690 control chromosomes in the GnomAD database, including 255,407 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 0.52 ( 21689 hom., cov: 32)

Exomes 𝑓: 0.56 ( 233718 hom. )

Consequence

CENPF
NM_016343.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.952

Publications

47 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: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, G2P, Genomics England PanelApp

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=6.1669925E-7).

BP6

Variant 1-214657274-A-G is Benign according to our data. Variant chr1-214657274-A-G is described in ClinVar as Benign. ClinVar VariationId is 1209683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPF	NM_016343.4	MANE Select	c.8827A>G	p.Arg2943Gly	missense	Exon 18 of 20	NP_057427.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CENPF	ENST00000366955.8	TSL:1 MANE Select	c.8827A>G	p.Arg2943Gly	missense	Exon 18 of 20	ENSP00000355922.3	P49454
CENPF	ENST00000934982.1		c.8947A>G	p.Arg2983Gly	missense	Exon 19 of 21	ENSP00000605041.1
CENPF	ENST00000934983.1		c.8827A>G	p.Arg2943Gly	missense	Exon 18 of 20	ENSP00000605042.1

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79601

AN:

151862

Hom.:

21675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.877

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.558

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.550

GnomAD2 exomes

AF:

0.606

AC:

151878

AN:

250824

AF XY:

0.605

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.723

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.884

Gnomad FIN exome

AF:

0.572

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.588

GnomAD4 exome

AF:

0.559

AC:

816928

AN:

1461710

Hom.:

233718

Cov.:

AF XY:

0.562

AC XY:

408903

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.378

AC:

12647

AN:

33474

American (AMR)

AF:

0.712

AC:

31845

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.550

AC:

14367

AN:

26132

East Asian (EAS)

AF:

0.879

AC:

34902

AN:

39694

South Asian (SAS)

AF:

0.704

AC:

60737

AN:

86252

European-Finnish (FIN)

AF:

0.574

AC:

30668

AN:

53398

Middle Eastern (MID)

AF:

0.610

AC:

3518

AN:

5768

European-Non Finnish (NFE)

AF:

0.534

AC:

594299

AN:

1111878

Other (OTH)

AF:

0.562

AC:

33945

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

21149

42298

63446

84595

105744

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17076

34152

51228

68304

85380

<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:

0.524

AC:

79647

AN:

151980

Hom.:

21689

Cov.:

AF XY:

0.531

AC XY:

39418

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.391

AC:

16223

AN:

41454

American (AMR)

AF:

0.636

AC:

9711

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.545

AC:

1889

AN:

3466

East Asian (EAS)

AF:

0.878

AC:

4523

AN:

5154

South Asian (SAS)

AF:

0.716

AC:

3447

AN:

4814

European-Finnish (FIN)

AF:

0.572

AC:

6046

AN:

10568

Middle Eastern (MID)

AF:

0.559

AC:

162

AN:

290

European-Non Finnish (NFE)

AF:

0.531

AC:

36105

AN:

67952

Other (OTH)

AF:

0.552

AC:

1160

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1885

3770

5655

7540

9425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.537

Hom.:

85613

Bravo

AF:

0.523

TwinsUK

AF:

0.544

AC:

2018

ALSPAC

AF:

0.539

AC:

2078

ESP6500AA

AF:

0.397

AC:

1750

ESP6500EA

AF:

0.541

AC:

4649

ExAC

AF:

0.598

AC:

72611

Asia WGS

AF:

0.777

AC:

2699

AN:

3478

EpiCase

AF:

0.534

EpiControl

AF:

0.545

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Stromme syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.4

(source)

DANN

Benign

0.68

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.34

MetaRNN

Benign

6.2e-7

MetaSVM

Benign

-1.1

PhyloP100

0.95

PrimateAI

Benign

0.20

PROVEAN

Benign

0.96

REVEL

Benign

0.033

Sift

Benign

0.66

Sift4G

Benign

0.25

Vest4

0.036

MPC

0.064

ClinPred

0.0058

GERP RS

2.5

Varity_R

0.036

gMVP

0.092

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over