1-214614216-A-G

Variant names:

• chr1-214614216-A-G
• rs148672580
• NM_016343.4:c.162+300A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016343.4(CENPF):​c.162+300A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 151,636 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.020 (46 hom., cov: 31)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.219
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-214614216-A-G is Benign according to our data. Variant chr1-214614216-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1190879.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0204 (3099/151636) while in subpopulation AFR AF = 0.043 (1776/41258). AF 95% confidence interval is 0.0414. There are 46 homozygotes in GnomAd4. There are 1499 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

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+300A>G		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+300A>G		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.162+300A>G		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.162+300A>G		intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3093 AN: 151522 Hom.: 46 Cov.: 31

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00928

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.00486

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.0204 AC: 3099 AN: 151636 Hom.: 46 Cov.: 31 AF XY: 0.0202 AC XY: 1499 AN XY: 74080

African (AFR) AF: 0.0430 AC: 1776 AN: 41258

American (AMR) AF: 0.00927 AC: 141 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.0369 AC: 177 AN: 4802

European-Finnish (FIN) AF: 0.00486 AC: 51 AN: 10488

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0134 AC: 908 AN: 67936

Other (OTH) AF: 0.0133 AC: 28 AN: 2104

Alfa AF: 0.0187 Hom.: 4

Bravo AF: 0.0205

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.50
PhyloP100		-0.22
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: rs148672580; hg19: chr1-214787559;