1-214651946-CTTT-CTTTT

Variant names:

• chr1-214651946-C-CT
• rs34322009
• NM_016343.4:c.8160+72dupT

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+72dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,133,906 control chromosomes in the GnomAD database, including 83 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (74 hom., cov: 27)
  • Exomes 𝑓: 0.038 (9 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-CT is Benign according to our data. Variant chr1-214651946-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1237449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0654 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+72dupT		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+61insT		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.8280+60_8280+61insT		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.8160+60_8160+61insT		intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 2836 AN: 140622 Hom.: 74 Cov.: 27

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00667

Gnomad ASJ AF: 0.000302

Gnomad EAS AF: 0.000409

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00156

Gnomad MID AF: 0.0176

Gnomad NFE AF: 0.000778

Gnomad OTH AF: 0.0162

GnomAD4 exome AF: 0.0383 AC: 38064 AN: 993260 Hom.: 9 AF XY: 0.0381 AC XY: 18541 AN XY: 487120

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

African (AFR) AF: 0.125 AC: 2802 AN: 22412

American (AMR) AF: 0.0451 AC: 737 AN: 16346

Ashkenazi Jewish (ASJ) AF: 0.0333 AC: 469 AN: 14082

East Asian (EAS) AF: 0.0281 AC: 797 AN: 28368

South Asian (SAS) AF: 0.0464 AC: 1949 AN: 41984

European-Finnish (FIN) AF: 0.0252 AC: 979 AN: 38894

Middle Eastern (MID) AF: 0.0333 AC: 136 AN: 4080

European-Non Finnish (NFE) AF: 0.0362 AC: 28466 AN: 785784

Other (OTH) AF: 0.0419 AC: 1729 AN: 41310

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0201 AC: 2833 AN: 140646 Hom.: 74 Cov.: 27 AF XY: 0.0199 AC XY: 1352 AN XY: 68022

African (AFR) AF: 0.0675 AC: 2640 AN: 39092

American (AMR) AF: 0.00666 AC: 93 AN: 13962

Ashkenazi Jewish (ASJ) AF: 0.000302 AC: 1 AN: 3314

East Asian (EAS) AF: 0.000411 AC: 2 AN: 4872

South Asian (SAS) AF: 0.00 AC: 0 AN: 4392

European-Finnish (FIN) AF: 0.00156 AC: 12 AN: 7706

Middle Eastern (MID) AF: 0.0191 AC: 5 AN: 262

European-Non Finnish (NFE) AF: 0.000763 AC: 49 AN: 64228

Other (OTH) AF: 0.0161 AC: 31 AN: 1926

Alfa AF: 0.00 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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34322009; hg19: chr1-214825289;