1-214614216-A-G

Position:

• chr1-214614216-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000366955.8(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 ENST00000366955.8 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.219

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPF	NM_016343.4	c.162+300A>G		intron_variant		ENST00000366955.8	NP_057427.3
CENPF	XM_011509082.4	c.162+300A>G		intron_variant			XP_011507384.1
CENPF	XM_017000086.3	c.162+300A>G		intron_variant			XP_016855575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8	c.162+300A>G		intron_variant		1	NM_016343.4	ENSP00000355922	P2
CENPF	ENST00000706765.1	c.162+300A>G		intron_variant				ENSP00000516538	A2
CENPF	ENST00000464322.5	n.330+300A>G		intron_variant, non_coding_transcript_variant		2
CENPF	ENST00000706764.1	n.340+300A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.00927

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.00486

Gnomad4 NFE AF: 0.0134

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0187 Hom.: 4

Bravo AF: 0.0205

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs148672580; hg19: chr1-214787559;