rs17023274

Variant names:

• chr1-214614200-A-G
• rs17023274
• NM_016343.4:c.162+284A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016343.4(CENPF):​c.162+284A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 149,688 control chromosomes in the GnomAD database, including 424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.070 (424 hom., cov: 31)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-214614200-A-G is Benign according to our data. Variant chr1-214614200-A-G is described in ClinVar as Benign. ClinVar VariationId is 1237184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPF	NM_016343.4	MANE Select	c.162+284A>G		intron	N/A	NP_057427.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPF	ENST00000366955.8	TSL:1 MANE Select	c.162+284A>G		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.162+284A>G		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.162+284A>G		intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10465 AN: 149574 Hom.: 424 Cov.: 31

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0514

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0540

Gnomad OTH AF: 0.0647

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0701 AC: 10491 AN: 149688 Hom.: 424 Cov.: 31 AF XY: 0.0713 AC XY: 5193 AN XY: 72832

African (AFR) AF: 0.0829 AC: 3366 AN: 40608

American (AMR) AF: 0.108 AC: 1601 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 178 AN: 3462

East Asian (EAS) AF: 0.121 AC: 616 AN: 5070

South Asian (SAS) AF: 0.144 AC: 683 AN: 4758

European-Finnish (FIN) AF: 0.0227 AC: 227 AN: 10010

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0540 AC: 3656 AN: 67704

Other (OTH) AF: 0.0654 AC: 136 AN: 2078

Alfa AF: 0.0656 Hom.: 171

Bravo AF: 0.0777

Asia WGS AF: 0.123 AC: 425 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.99
DANN	Benign	0.56
PhyloP100		-0.066
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17023274; hg19: chr1-214787543;