chr1-214657274-A-G

Position:

• chr1-214657274-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016343.4(CENPF):​c.8827A>G​(p.Arg2943Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,613,690 control chromosomes in the GnomAD database, including 255,407 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21689 hom., cov: 32)
  • Exomes 𝑓: 0.56 (233718 hom.)
• Consequence: CENPF NM_016343.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.952

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.1669925E-7).
• BP6: Variant 1-214657274-A-G is Benign according to our data. Variant chr1-214657274-A-G is described in ClinVar as [Benign]. Clinvar id is 1209683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPF	NM_016343.4	c.8827A>G	p.Arg2943Gly	missense_variant	18/20	ENST00000366955.8	NP_057427.3
CENPF	XM_017000086.3	c.8827A>G	p.Arg2943Gly	missense_variant	18/20		XP_016855575.1
CENPF	XM_011509082.4	c.8650A>G	p.Arg2884Gly	missense_variant	17/19		XP_011507384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8	c.8827A>G	p.Arg2943Gly	missense_variant	18/20	1	NM_016343.4	ENSP00000355922.3
CENPF	ENST00000706765.1	c.8650A>G	p.Arg2884Gly	missense_variant	17/19			ENSP00000516538.1
CENPF	ENST00000469862.1	n.598A>G		non_coding_transcript_exon_variant	2/2	2
CENPF	ENST00000706766.1	n.926A>G		non_coding_transcript_exon_variant	3/5

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79601 AN: 151862 Hom.: 21675 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.550

GnomAD3 exomes AF: 0.606 AC: 151878 AN: 250824 Hom.: 47850 AF XY: 0.605 AC XY: 82062 AN XY: 135580

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.557

Gnomad EAS exome AF: 0.884

Gnomad SAS exome AF: 0.707

Gnomad FIN exome AF: 0.572

Gnomad NFE exome AF: 0.540

Gnomad OTH exome AF: 0.588

GnomAD4 exome AF: 0.559 AC: 816928 AN: 1461710 Hom.: 233718 Cov.: 53 AF XY: 0.562 AC XY: 408903 AN XY: 727156

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.550

Gnomad4 EAS exome AF: 0.879

Gnomad4 SAS exome AF: 0.704

Gnomad4 FIN exome AF: 0.574

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.524 AC: 79647 AN: 151980 Hom.: 21689 Cov.: 32 AF XY: 0.531 AC XY: 39418 AN XY: 74290

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.552

Alfa AF: 0.540 Hom.: 56316

Bravo AF: 0.523

TwinsUK AF: 0.544 AC: 2018

ALSPAC AF: 0.539 AC: 2078

ESP6500AA AF: 0.397 AC: 1750

ESP6500EA AF: 0.541 AC: 4649

ExAC AF: 0.598 AC: 72611

Asia WGS AF: 0.777 AC: 2699 AN: 3478

EpiCase AF: 0.534

EpiControl AF: 0.545

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 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
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.68
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	6.2e-7	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.96	N
REVEL	Benign	0.033
Sift	Benign	0.66	T
Sift4G	Benign	0.25	T
Vest4		0.036
MPC		0.064
ClinPred		0.0058	T
GERP RS		2.5
Varity_R		0.036
gMVP		0.092

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: rs438034; hg19: chr1-214830617;