chr16-2435662-CACACATATATATAT-C

Variant names:

• chr16-2435662-CACACATATATATAT-C
• rs1434595689
• NM_001761.3:c.279-142_279-129delCACATATATATATA

Variant summary

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

The NM_001761.3(CCNF):​c.279-142_279-129delCACATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (16 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCNF NM_001761.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.181
• Publications: 0 publications found

Genes affected

CCNF (HGNC:1591): (cyclin F) This gene encodes a member of the cyclin family. Cyclins are important regulators of cell cycle transitions through their ability to bind and activate cyclin-dependent protein kinases. This member also belongs to the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and it was one of the first proteins in which the F-box motif was identified. [provided by RefSeq, Jul 2008]

CCNF Gene-Disease associations (from GenCC):

• frontotemporal dementia and/or amyotrophic lateral sclerosis 5

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

ENSG00000285970 (HGNC:):

ACMG classification

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

• BP6: Variant 16-2435662-CACACATATATATAT-C is Benign according to our data. Variant chr16-2435662-CACACATATATATAT-C is described in ClinVar as Benign. ClinVar VariationId is 1249938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001761.3. 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
	CCNF	NM_001761.3	MANE Select	c.279-142_279-129delCACATATATATATA		intron	N/A	NP_001752.2	P41002
	CCNF	NM_001323538.2		c.-646-142_-646-129delCACATATATATATA		intron	N/A	NP_001310467.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNF	ENST00000397066.9	TSL:1 MANE Select	c.279-143_279-130delACACATATATATAT		intron	N/A	ENSP00000380256.4	P41002
	CCNF	ENST00000293968.11	TSL:1	n.172-143_172-130delACACATATATATAT		intron	N/A	ENSP00000293968.7	H0Y2P7
	CCNF	ENST00000916916.1		c.279-143_279-130delACACATATATATAT		intron	N/A	ENSP00000586975.1

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 786 AN: 26792 Hom.: 16 Cov.: 0

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000270

Gnomad OTH AF: 0.0276

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 36092 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20564

African (AFR) AF: 0.00 AC: 0 AN: 590

American (AMR) AF: 0.00 AC: 0 AN: 1222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 954

East Asian (EAS) AF: 0.00 AC: 0 AN: 2662

South Asian (SAS) AF: 0.00 AC: 0 AN: 1566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 152

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 23622

Other (OTH) AF: 0.00 AC: 0 AN: 1892

GnomAD4 genome AF: 0.0293 AC: 787 AN: 26842 Hom.: 16 Cov.: 0 AF XY: 0.0273 AC XY: 337 AN XY: 12348

African (AFR) AF: 0.0687 AC: 755 AN: 10994

American (AMR) AF: 0.0108 AC: 19 AN: 1762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 896

East Asian (EAS) AF: 0.00 AC: 0 AN: 108

South Asian (SAS) AF: 0.00 AC: 0 AN: 396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 74

European-Non Finnish (NFE) AF: 0.000270 AC: 3 AN: 11114

Other (OTH) AF: 0.0276 AC: 10 AN: 362

Alfa AF: 0.00 Hom.: 0

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		0.18
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1434595689; hg19: chr16-2485663;