rs3748697

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.7186A>G(p.Asn2396Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,612,922 control chromosomes in the GnomAD database, including 185,145 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 0.36 ( 12355 hom., cov: 33)

Exomes 𝑓: 0.47 ( 172790 hom. )

Consequence

CENPF
NM_016343.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.224

Publications

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

CENPF links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_016343.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=2.8148293E-4).

BP6

Variant 1-214646756-A-G is Benign according to our data. Variant chr1-214646756-A-G is described in ClinVar as Benign. ClinVar VariationId is 1209678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 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.7186A>G	p.Asn2396Asp	missense	Exon 13 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.7186A>G	p.Asn2396Asp	missense	Exon 13 of 20	ENSP00000355922.3	P49454
CENPF	ENST00000934982.1		c.7306A>G	p.Asn2436Asp	missense	Exon 14 of 21	ENSP00000605041.1
CENPF	ENST00000934983.1		c.7186A>G	p.Asn2396Asp	missense	Exon 13 of 20	ENSP00000605042.1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54767

AN:

152054

Hom.:

12356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.552

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.519

Gnomad OTH

AF:

0.380

GnomAD2 exomes

AF:

0.391

AC:

97511

AN:

249190

AF XY:

0.402

show subpopulations

Gnomad AFR exome

AF:

0.0980

Gnomad AMR exome

AF:

0.261

Gnomad ASJ exome

AF:

0.494

Gnomad EAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.512

Gnomad OTH exome

AF:

0.428

GnomAD4 exome

AF:

0.474

AC:

691912

AN:

1460750

Hom.:

172790

Cov.:

AF XY:

0.472

AC XY:

342742

AN XY:

726696

show subpopulations

African (AFR)

AF:

0.0904

AC:

3019

AN:

33406

American (AMR)

AF:

0.268

AC:

11939

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

12856

AN:

26088

East Asian (EAS)

AF:

0.134

AC:

5325

AN:

39688

South Asian (SAS)

AF:

0.326

AC:

28063

AN:

86090

European-Finnish (FIN)

AF:

0.448

AC:

23914

AN:

53352

Middle Eastern (MID)

AF:

0.401

AC:

2306

AN:

5756

European-Non Finnish (NFE)

AF:

0.520

AC:

577744

AN:

1111464

Other (OTH)

AF:

0.443

AC:

26746

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

19122

38244

57366

76488

95610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16102

32204

48306

64408

80510

<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:

0.360

AC:

54768

AN:

152172

Hom.:

12355

Cov.:

AF XY:

0.355

AC XY:

26404

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.108

AC:

4487

AN:

41528

American (AMR)

AF:

0.328

AC:

5018

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

1722

AN:

3464

East Asian (EAS)

AF:

0.122

AC:

631

AN:

5180

South Asian (SAS)

AF:

0.312

AC:

1508

AN:

4828

European-Finnish (FIN)

AF:

0.446

AC:

4714

AN:

10570

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.519

AC:

35271

AN:

67992

Other (OTH)

AF:

0.379

AC:

803

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1573

3146

4718

6291

7864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.461

Hom.:

86066

Bravo

AF:

0.339

Asia WGS

AF:

0.201

AC:

704

AN:

3478

EpiCase

AF:

0.512

EpiControl

AF:

0.507

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

0.12

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.5

(source)

DANN

Benign

0.77

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.57

MetaRNN

Benign

0.00028

MetaSVM

Benign

-0.92

PhyloP100

0.22

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.80

REVEL

Benign

0.14

Sift

Benign

0.55

Sift4G

Benign

0.70

Varity_R

0.055

gMVP

0.045

Mutation Taster

=91/9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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