1-214651946-CTTTTT-CTTTTTTT

Variant names:

• chr1-214651946-C-CTT
• rs34322009
• NM_016343.4:c.8160+71_8160+72dupTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016343.4(CENPF):​c.8160+71_8160+72dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,160,990 control chromosomes in the GnomAD database, including 3,199 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2661 hom., cov: 27)
  • Exomes 𝑓: 0.082 (538 hom.)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.169
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, G2P, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-214651946-C-CTT is Benign according to our data. Variant chr1-214651946-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 1230353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 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.8160+71_8160+72dupTT		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.8160+60_8160+61insTT		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.8280+60_8280+61insTT		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.8160+60_8160+61insTT		intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 22984 AN: 140570 Hom.: 2655 Cov.: 27

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.0404

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0315

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.0948

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.0818 AC: 83487 AN: 1020396 Hom.: 538 AF XY: 0.0814 AC XY: 40740 AN XY: 500662

African (AFR) AF: 0.262 AC: 5997 AN: 22870

American (AMR) AF: 0.0884 AC: 1479 AN: 16724

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 1327 AN: 14530

East Asian (EAS) AF: 0.0247 AC: 740 AN: 30008

South Asian (SAS) AF: 0.0738 AC: 3162 AN: 42842

European-Finnish (FIN) AF: 0.0874 AC: 3496 AN: 40008

Middle Eastern (MID) AF: 0.158 AC: 664 AN: 4192

European-Non Finnish (NFE) AF: 0.0777 AC: 62714 AN: 806762

Other (OTH) AF: 0.0920 AC: 3908 AN: 42460

GnomAD4 genome AF: 0.164 AC: 23012 AN: 140594 Hom.: 2661 Cov.: 27 AF XY: 0.161 AC XY: 10971 AN XY: 68016

African (AFR) AF: 0.339 AC: 13241 AN: 39048

American (AMR) AF: 0.114 AC: 1593 AN: 13956

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 385 AN: 3314

East Asian (EAS) AF: 0.0316 AC: 154 AN: 4872

South Asian (SAS) AF: 0.107 AC: 469 AN: 4388

European-Finnish (FIN) AF: 0.0926 AC: 713 AN: 7700

Middle Eastern (MID) AF: 0.149 AC: 39 AN: 262

European-Non Finnish (NFE) AF: 0.0948 AC: 6092 AN: 64240

Other (OTH) AF: 0.151 AC: 290 AN: 1922

Alfa AF: 0.0177 Hom.: 16

ClinVar

ClinVar submissions

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
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34322009; hg19: chr1-214825289;