1-214651946-CTTTTT-CTTTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016343.4(CENPF):​c.8160+72delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,046,196 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 27)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Variant has high frequency in the EAS (0.261) population. However there is too low homozygotes in high coverage region: (expected more than 4076, got 0).

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+72delT		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+61delT		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.8280+61delT		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.8160+61delT		intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 183 AN: 140428 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000646

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00184

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.00550

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000951

Gnomad OTH AF: 0.00104

GnomAD4 exome AF: 0.144 AC: 130418 AN: 905750 Hom.: 0 AF XY: 0.148 AC XY: 65792 AN XY: 443322

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

African (AFR) AF: 0.0645 AC: 1408 AN: 21836

American (AMR) AF: 0.195 AC: 2875 AN: 14712

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 2239 AN: 12168

East Asian (EAS) AF: 0.267 AC: 5960 AN: 22354

South Asian (SAS) AF: 0.172 AC: 6791 AN: 39462

European-Finnish (FIN) AF: 0.217 AC: 6394 AN: 29498

Middle Eastern (MID) AF: 0.0946 AC: 351 AN: 3712

European-Non Finnish (NFE) AF: 0.136 AC: 98611 AN: 724498

Other (OTH) AF: 0.154 AC: 5789 AN: 37510

⚠️ 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: 0.00132 AC: 186 AN: 140446 Hom.: 0 Cov.: 27 AF XY: 0.00133 AC XY: 90 AN XY: 67890

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

African (AFR) AF: 0.00153 AC: 60 AN: 39108

American (AMR) AF: 0.000645 AC: 9 AN: 13950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3312

East Asian (EAS) AF: 0.00185 AC: 9 AN: 4868

South Asian (SAS) AF: 0.000455 AC: 2 AN: 4394

European-Finnish (FIN) AF: 0.00550 AC: 42 AN: 7630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 262

European-Non Finnish (NFE) AF: 0.000952 AC: 61 AN: 64106

Other (OTH) AF: 0.00156 AC: 3 AN: 1924

⚠️ 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.: 16

ClinVar

Not reported in ClinVar

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)		0.010		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; COSMIC: COSV65275123; COSMIC: COSV65275123;