1-214614108-CTTT-CTTTTT

Variant names:

• chr1-214614108-C-CTT
• rs370473275
• NM_016343.4:c.162+204_162+205dupTT

Variant summary

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

The NM_016343.4(CENPF):​c.162+204_162+205dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.027 (188 hom., cov: 0)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.288
• 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 1-214614108-C-CTT is Benign according to our data. Variant chr1-214614108-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 1183371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0967 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+204_162+205dupTT		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+192_162+193insTT		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.162+192_162+193insTT		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.162+192_162+193insTT		intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.0272 AC: 3343 AN: 123024 Hom.: 188 Cov.: 0

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000236

Gnomad SAS AF: 0.000533

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00370

Gnomad NFE AF: 0.000505

Gnomad OTH AF: 0.0155

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

GnomAD4 genome AF: 0.0272 AC: 3346 AN: 123014 Hom.: 188 Cov.: 0 AF XY: 0.0250 AC XY: 1470 AN XY: 58696

African (AFR) AF: 0.0996 AC: 3139 AN: 31512

American (AMR) AF: 0.0122 AC: 147 AN: 12030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3108

East Asian (EAS) AF: 0.000237 AC: 1 AN: 4222

South Asian (SAS) AF: 0.000536 AC: 2 AN: 3734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6234

Middle Eastern (MID) AF: 0.00410 AC: 1 AN: 244

European-Non Finnish (NFE) AF: 0.000505 AC: 30 AN: 59414

Other (OTH) AF: 0.0154 AC: 26 AN: 1684

Alfa AF: 0.00 Hom.: 3

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		-0.29
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: rs370473275; hg19: chr1-214787451;