rs3790648

chr1-214647151-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016343.4(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 NM_016343.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.518

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]

ACMG classification

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	UniProt
CENPF	NM_016343.4	c.7581G>A	p.Leu2527=	synonymous_variant	13/20	ENST00000366955.8
CENPF	XM_017000086.3	c.7581G>A	p.Leu2527=	synonymous_variant	13/20
CENPF	XM_011509082.4	c.7581G>A	p.Leu2527=	synonymous_variant	13/19

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11208 AN: 152144 Hom.: 509 Cov.: 33

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

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.: 34 AF XY: 0.0640 AC XY: 46564 AN XY: 727020

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.: 33 AF XY: 0.0744 AC XY: 5538 AN XY: 74432

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 23, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2018	- -

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

Other links and lift over

dbSNP: rs3790648; hg19: chr1-214820494; COSMIC: COSV65277749; COSMIC: COSV65277749;