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GeneBe

1-214613787-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_016343.4(CENPF):c.33G>A(p.Gly11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,607,980 control chromosomes in the GnomAD database, including 189,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 12687 hom., cov: 32)
Exomes 𝑓: 0.48 ( 176929 hom. )

Consequence

CENPF
NM_016343.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.213
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-214613787-G-A is Benign according to our data. Variant chr1-214613787-G-A is described in ClinVar as [Benign]. Clinvar id is 1209807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.213 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CENPFNM_016343.4 linkuse as main transcriptc.33G>A p.Gly11= synonymous_variant 2/20 ENST00000366955.8
CENPFXM_017000086.3 linkuse as main transcriptc.33G>A p.Gly11= synonymous_variant 2/20
CENPFXM_011509082.4 linkuse as main transcriptc.33G>A p.Gly11= synonymous_variant 2/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CENPFENST00000366955.8 linkuse as main transcriptc.33G>A p.Gly11= synonymous_variant 2/201 NM_016343.4 P2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.364
AC:
55368
AN:
151948
Hom.:
12688
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.109
Gnomad AMI
AF:
0.552
Gnomad AMR
AF:
0.330
Gnomad ASJ
AF:
0.496
Gnomad EAS
AF:
0.119
Gnomad SAS
AF:
0.307
Gnomad FIN
AF:
0.459
Gnomad MID
AF:
0.373
Gnomad NFE
AF:
0.526
Gnomad OTH
AF:
0.382
GnomAD3 exomes
AF:
0.397
AC:
97610
AN:
245878
Hom.:
22388
AF XY:
0.409
AC XY:
54355
AN XY:
132988
show subpopulations
Gnomad AFR exome
AF:
0.0981
Gnomad AMR exome
AF:
0.262
Gnomad ASJ exome
AF:
0.494
Gnomad EAS exome
AF:
0.117
Gnomad SAS exome
AF:
0.325
Gnomad FIN exome
AF:
0.463
Gnomad NFE exome
AF:
0.520
Gnomad OTH exome
AF:
0.434
GnomAD4 exome
AF:
0.480
AC:
698572
AN:
1455914
Hom.:
176929
Cov.:
36
AF XY:
0.477
AC XY:
345750
AN XY:
724178
show subpopulations
Gnomad4 AFR exome
AF:
0.0906
Gnomad4 AMR exome
AF:
0.269
Gnomad4 ASJ exome
AF:
0.493
Gnomad4 EAS exome
AF:
0.130
Gnomad4 SAS exome
AF:
0.326
Gnomad4 FIN exome
AF:
0.459
Gnomad4 NFE exome
AF:
0.527
Gnomad4 OTH exome
AF:
0.446
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.364
AC:
55368
AN:
152066
Hom.:
12687
Cov.:
32
AF XY:
0.359
AC XY:
26663
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.109
Gnomad4 AMR
AF:
0.329
Gnomad4 ASJ
AF:
0.496
Gnomad4 EAS
AF:
0.118
Gnomad4 SAS
AF:
0.309
Gnomad4 FIN
AF:
0.459
Gnomad4 NFE
AF:
0.526
Gnomad4 OTH
AF:
0.382
Alfa
AF:
0.464
Hom.:
13006
Bravo
AF:
0.342
Asia WGS
AF:
0.197
AC:
689
AN:
3478
EpiCase
AF:
0.521
EpiControl
AF:
0.510

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 07, 2018- -
Stromme syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
8.9
Dann
Benign
0.83
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2070064; hg19: chr1-214787130; COSMIC: COSV65273614; COSMIC: COSV65273614; API