1-214614184-G-C

Variant names:

• chr1-214614184-G-C
• rs12734998
• NM_016343.4:c.162+268G>C

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+268G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 144,192 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.017 (32 hom., cov: 31)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.268
• 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-214614184-G-C is Benign according to our data. Variant chr1-214614184-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1218534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0172 (2479/144192) while in subpopulation AMR AF = 0.0241 (327/13556). AF 95% confidence interval is 0.023. There are 32 homozygotes in GnomAd4. There are 1147 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 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+268G>C		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+268G>C		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.162+268G>C		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.162+268G>C		intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2478 AN: 144054 Hom.: 32 Cov.: 31

Gnomad AFR AF: 0.00564

Gnomad AMI AF: 0.0321

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.0247

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00874

Gnomad FIN AF: 0.0128

Gnomad MID AF: 0.0347

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0241

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

GnomAD4 genome AF: 0.0172 AC: 2479 AN: 144192 Hom.: 32 Cov.: 31 AF XY: 0.0165 AC XY: 1147 AN XY: 69616

African (AFR) AF: 0.00563 AC: 217 AN: 38570

American (AMR) AF: 0.0241 AC: 327 AN: 13556

Ashkenazi Jewish (ASJ) AF: 0.0247 AC: 85 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 4800

South Asian (SAS) AF: 0.00894 AC: 41 AN: 4586

European-Finnish (FIN) AF: 0.0128 AC: 114 AN: 8936

Middle Eastern (MID) AF: 0.0341 AC: 9 AN: 264

European-Non Finnish (NFE) AF: 0.0240 AC: 1609 AN: 67118

Other (OTH) AF: 0.0239 AC: 48 AN: 2012

Alfa AF: 0.0182 Hom.: 5

Bravo AF: 0.0167

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.85
CADD	Benign	7.9
DANN	Benign	0.72
PhyloP100		0.27
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: rs12734998; hg19: chr1-214787527;