Genetic Variant CENPF:c.8160+70_8160+72dupTTT (chr1-214651946-C-CTTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016343.4(CENPF):c.8160+70_8160+72dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,167,296 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

CENPF
NM_016343.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.169

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.8160+70_8160+72dupTTT		intron	N/A	NP_057427.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CENPF	ENST00000366955.8	TSL:1 MANE Select	c.8160+60_8160+61insTTT	intron	N/A	ENSP00000355922.3	P49454
CENPF	ENST00000934982.1		c.8280+60_8280+61insTTT	intron	N/A	ENSP00000605041.1
CENPF	ENST00000934983.1		c.8160+60_8160+61insTTT	intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes

AF:

0.000327

AC:

AN:

140702

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000359

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000215

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000679

Gnomad FIN

AF:

0.000130

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000342

Gnomad OTH

AF:

0.00156

GnomAD4 exome

AF:

0.00160

AC:

1646

AN:

1026570

Hom.:

AF XY:

0.00159

AC XY:

800

AN XY:

503792

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00894

AC:

207

AN:

23146

American (AMR)

AF:

0.00184

AC:

AN:

16886

Ashkenazi Jewish (ASJ)

AF:

0.00170

AC:

AN:

14680

East Asian (EAS)

AF:

0.000232

AC:

AN:

30134

South Asian (SAS)

AF:

0.00200

AC:

AN:

43090

European-Finnish (FIN)

AF:

0.000767

AC:

AN:

40424

Middle Eastern (MID)

AF:

0.00519

AC:

AN:

4236

European-Non Finnish (NFE)

AF:

0.00142

AC:

1149

AN:

811170

Other (OTH)

AF:

0.00206

AC:

AN:

42804

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.307

Heterozygous variant carriers

127

254

382

509

636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

162

216

270

<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:

0.000327

AC:

AN:

140726

Hom.:

Cov.:

AF XY:

0.000308

AC XY:

AN XY:

68082

show subpopulations

African (AFR)

AF:

0.000358

AC:

AN:

39116

American (AMR)

AF:

0.000215

AC:

AN:

13970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3316

East Asian (EAS)

AF:

0.00

AC:

AN:

4872

South Asian (SAS)

AF:

0.000683

AC:

AN:

4394

European-Finnish (FIN)

AF:

0.000130

AC:

AN:

7708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

262

European-Non Finnish (NFE)

AF:

0.000342

AC:

AN:

64268

Other (OTH)

AF:

0.00156

AC:

AN:

1928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-214651946-CTTTTT-CTTTTTTTT

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