1-214614108-CTTT-CTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016343.4(CENPF):​c.162+205delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00092 (0 hom., cov: 0)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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+205delT		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+193delT		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.162+193delT		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.162+193delT		intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.000911 AC: 112 AN: 122992 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000666

Gnomad ASJ AF: 0.00129

Gnomad EAS AF: 0.000943

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00115

Gnomad OTH AF: 0.00179

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

GnomAD4 genome AF: 0.000919 AC: 113 AN: 122982 Hom.: 0 Cov.: 0 AF XY: 0.00111 AC XY: 65 AN XY: 58680

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000349 AC: 11 AN: 31538

American (AMR) AF: 0.000665 AC: 8 AN: 12030

Ashkenazi Jewish (ASJ) AF: 0.00129 AC: 4 AN: 3102

East Asian (EAS) AF: 0.000947 AC: 4 AN: 4222

South Asian (SAS) AF: 0.00214 AC: 8 AN: 3734

European-Finnish (FIN) AF: 0.00112 AC: 7 AN: 6232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.00115 AC: 68 AN: 59366

Other (OTH) AF: 0.00178 AC: 3 AN: 1682

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism

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;