1-214614108-CTTT-CTTTT

Variant names:

• chr1-214614108-C-CT
• rs370473275
• NM_016343.4:c.162+205dupT

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+205dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (2087 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Illumina

ACMG classification

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

• BP6: Variant 1-214614108-C-CT is Benign according to our data. Variant chr1-214614108-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1249271.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 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+205dupT		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+193insT		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.162+192_162+193insT		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.162+192_162+193insT		intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 16372 AN: 122984 Hom.: 2080 Cov.: 0

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.0445

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0647

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0926

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.133 AC: 16389 AN: 122974 Hom.: 2087 Cov.: 0 AF XY: 0.133 AC XY: 7811 AN XY: 58684

African (AFR) AF: 0.335 AC: 10574 AN: 31528

American (AMR) AF: 0.117 AC: 1407 AN: 12020

Ashkenazi Jewish (ASJ) AF: 0.0647 AC: 201 AN: 3106

East Asian (EAS) AF: 0.120 AC: 508 AN: 4218

South Asian (SAS) AF: 0.112 AC: 420 AN: 3734

European-Finnish (FIN) AF: 0.0265 AC: 165 AN: 6234

Middle Eastern (MID) AF: 0.0943 AC: 23 AN: 244

European-Non Finnish (NFE) AF: 0.0482 AC: 2861 AN: 59374

Other (OTH) AF: 0.115 AC: 193 AN: 1684

Alfa AF: 0.00823 Hom.: 3

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
PhyloP100		-0.29
Mutation Taster		=100/0	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: rs370473275; hg19: chr1-214787451; COSMIC: COSV65274069; COSMIC: COSV65274069;