Variant rs3790648 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000366955.8(CENPF):c.7581G>A(p.Leu2527=) 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
ENST00000366955.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.518

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein
CENPF	NM_016343.4 linkuse as main transcript	c.7581G>A	p.Leu2527=	synonymous_variant	13/20	ENST00000366955.8	NP_057427.3
CENPF	XM_017000086.3 linkuse as main transcript	c.7581G>A	p.Leu2527=	synonymous_variant	13/20		XP_016855575.1
CENPF	XM_011509082.4 linkuse as main transcript	c.7581G>A	p.Leu2527=	synonymous_variant	13/19		XP_011507384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8 linkuse as main transcript	c.7581G>A	p.Leu2527=	synonymous_variant	13/20	1	NM_016343.4	ENSP00000355922	P2
CENPF	ENST00000706765.1 linkuse as main transcript	c.7581G>A	p.Leu2527=	synonymous_variant	13/19			ENSP00000516538	A2

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

GnomAD3 exomes

AF:

0.0833

AC:

20856

AN:

250344

Hom.:

1201

AF XY:

0.0820

AC XY:

11100

AN XY:

135344

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 SAS exome

AF:

0.149

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

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.0517

Gnomad4 EAS exome

AF:

0.115

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.0267

Gnomad4 NFE exome

AF:

0.0505

Gnomad4 OTH exome

AF:

0.0665

GnomAD4 genome

AF:

0.0739

AC:

11246

AN:

152260

Hom.:

511

Cov.:

AF XY:

0.0744

AC XY:

5538

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.0218

Gnomad4 NFE

AF:

0.0500

Gnomad4 OTH

AF:

0.0709

Alfa

AF:

0.0576

Hom.:

387

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2024	- -

Stromme syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.12

DANN

Benign

0.57

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over