chr1-214647151-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016343.4(CENPF):c.7581G>A(p.Leu2527Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 1,613,690 control chromosomes in the GnomAD database, including 4,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 511 hom., cov: 33)

Exomes 𝑓: 0.062 ( 3715 hom. )

Consequence

CENPF
NM_016343.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.518

Publications

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

CENPF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-214647151-G-A is Benign according to our data. Variant chr1-214647151-G-A is described in ClinVar as Benign. ClinVar VariationId is 1209680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.518 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPF	NM_016343.4 link	c.7581G>A	p.Leu2527Leu	synonymous_variant	Exon 13 of 20	ENST00000366955.8	NP_057427.3	P49454
CENPF	XM_017000086.3 link	c.7581G>A	p.Leu2527Leu	synonymous_variant	Exon 13 of 20		XP_016855575.1	P49454
CENPF	XM_011509082.4 link	c.7581G>A	p.Leu2527Leu	synonymous_variant	Exon 13 of 19		XP_011507384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8 link	c.7581G>A	p.Leu2527Leu	synonymous_variant	Exon 13 of 20	1	NM_016343.4	ENSP00000355922.3		P49454
CENPF	ENST00000706765.1 link	c.7581G>A	p.Leu2527Leu	synonymous_variant	Exon 13 of 19			ENSP00000516538.1		A0A9L9PXU7

Frequencies

GnomAD3 genomes

AF:

0.0737

AC:

11208

AN:

152144

Hom.:

509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0500

Gnomad OTH

AF:

0.0697

GnomAD2 exomes

AF:

0.0833

AC:

20856

AN:

250344

AF XY:

0.0820

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.0542

Gnomad EAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.0252

Gnomad NFE exome

AF:

0.0489

Gnomad OTH exome

AF:

0.0650

GnomAD4 exome

AF:

0.0622

AC:

90950

AN:

1461430

Hom.:

3715

Cov.:

AF XY:

0.0640

AC XY:

46564

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.108

AC:

3598

AN:

33468

American (AMR)

AF:

0.148

AC:

6630

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0517

AC:

1351

AN:

26124

East Asian (EAS)

AF:

0.115

AC:

4581

AN:

39668

South Asian (SAS)

AF:

0.148

AC:

12750

AN:

86212

European-Finnish (FIN)

AF:

0.0267

AC:

1427

AN:

53404

Middle Eastern (MID)

AF:

0.0732

AC:

422

AN:

5764

European-Non Finnish (NFE)

AF:

0.0505

AC:

56174

AN:

1111714

Other (OTH)

AF:

0.0665

AC:

4017

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

4118

8235

12353

16470

20588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2314

4628

6942

9256

11570

<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:

0.0739

AC:

11246

AN:

152260

Hom.:

511

Cov.:

AF XY:

0.0744

AC XY:

5538

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.104

AC:

4329

AN:

41554

American (AMR)

AF:

0.108

AC:

1646

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0521

AC:

181

AN:

3472

East Asian (EAS)

AF:

0.111

AC:

573

AN:

5178

South Asian (SAS)

AF:

0.142

AC:

683

AN:

4818

European-Finnish (FIN)

AF:

0.0218

AC:

231

AN:

10604

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0500

AC:

3400

AN:

68018

Other (OTH)

AF:

0.0709

AC:

150

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

523

1045

1568

2090

2613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0603

Hom.:

523

Bravo

AF:

0.0825

Asia WGS

AF:

0.119

AC:

413

AN:

3478

EpiCase

AF:

0.0506

EpiControl

AF:

0.0522

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Stromme syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.12

(source)

DANN

Benign

0.57

PhyloP100

-0.52

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over