chr1-214652853-G-A

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.8186G>A(p.Arg2729Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,593,726 control chromosomes in the GnomAD database, including 171,079 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 0.44 ( 15480 hom., cov: 32)

Exomes 𝑓: 0.45 ( 155599 hom. )

Consequence

CENPF
NM_016343.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0270

Publications

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

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=6.06294E-7).

BP6

Variant 1-214652853-G-A is Benign according to our data. Variant chr1-214652853-G-A is described in ClinVar as Benign. ClinVar VariationId is 1209682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 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.8186G>A	p.Arg2729Gln	missense	Exon 16 of 20	NP_057427.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CENPF	ENST00000366955.8	TSL:1 MANE Select	c.8186G>A	p.Arg2729Gln	missense	Exon 16 of 20	ENSP00000355922.3
CENPF	ENST00000934982.1		c.8306G>A	p.Arg2769Gln	missense	Exon 17 of 21	ENSP00000605041.1
CENPF	ENST00000934983.1		c.8186G>A	p.Arg2729Gln	missense	Exon 16 of 20	ENSP00000605042.1

Frequencies

GnomAD3 genomes

AF:

0.436

AC:

66150

AN:

151652

Hom.:

15473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.406

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.878

Gnomad SAS

AF:

0.654

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.469

GnomAD2 exomes

AF:

0.519

AC:

121624

AN:

234268

AF XY:

0.517

show subpopulations

Gnomad AFR exome

AF:

0.308

Gnomad AMR exome

AF:

0.681

Gnomad ASJ exome

AF:

0.472

Gnomad EAS exome

AF:

0.887

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.428

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.452

AC:

651614

AN:

1441958

Hom.:

155599

Cov.:

AF XY:

0.457

AC XY:

327290

AN XY:

716946

show subpopulations

African (AFR)

AF:

0.300

AC:

9613

AN:

32018

American (AMR)

AF:

0.663

AC:

26446

AN:

39888

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

11794

AN:

25236

East Asian (EAS)

AF:

0.883

AC:

34914

AN:

39544

South Asian (SAS)

AF:

0.634

AC:

51962

AN:

81910

European-Finnish (FIN)

AF:

0.492

AC:

26132

AN:

53146

Middle Eastern (MID)

AF:

0.518

AC:

2901

AN:

5602

European-Non Finnish (NFE)

AF:

0.416

AC:

460073

AN:

1105106

Other (OTH)

AF:

0.467

AC:

27779

AN:

59508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

15028

30055

45083

60110

75138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14414

28828

43242

57656

72070

<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:

0.436

AC:

66182

AN:

151768

Hom.:

15480

Cov.:

AF XY:

0.447

AC XY:

33159

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.314

AC:

12959

AN:

41334

American (AMR)

AF:

0.579

AC:

8821

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

1592

AN:

3472

East Asian (EAS)

AF:

0.879

AC:

4544

AN:

5172

South Asian (SAS)

AF:

0.652

AC:

3139

AN:

4814

European-Finnish (FIN)

AF:

0.491

AC:

5168

AN:

10522

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.419

AC:

28456

AN:

67898

Other (OTH)

AF:

0.472

AC:

994

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1835

3670

5504

7339

9174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.440

Hom.:

50973

Bravo

AF:

0.438

TwinsUK

AF:

0.419

AC:

1554

ALSPAC

AF:

0.416

AC:

1605

ESP6500AA

AF:

0.318

AC:

1400

ESP6500EA

AF:

0.429

AC:

3691

ExAC

AF:

0.515

AC:

62482

Asia WGS

AF:

0.747

AC:

2590

AN:

3478

EpiCase

AF:

0.429

EpiControl

AF:

0.439

ClinVar

ClinVar submissions as Germline

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

0.058

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0070

(source)

DANN

Benign

0.13

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.64

MetaRNN

Benign

6.1e-7

MetaSVM

Benign

-1.0

PhyloP100

-0.027

PrimateAI

Benign

0.25

PROVEAN

Benign

0.66

REVEL

Benign

0.054

Sift

Benign

0.69

Sift4G

Benign

0.66

Vest4

0.030

MPC

0.060

ClinPred

0.000022

GERP RS

-6.4

Varity_R

0.017

gMVP

0.0069

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over