chr1-214614200-A-G

Position:

• chr1-214614200-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000366955.8(CENPF):​c.162+284A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 149,688 control chromosomes in the GnomAD database, including 424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.070 (424 hom., cov: 31)
• Consequence: CENPF ENST00000366955.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660

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=-0.89).
• BP6: Variant 1-214614200-A-G is Benign according to our data. Variant chr1-214614200-A-G is described in ClinVar as [Benign]. Clinvar id is 1237184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPF	NM_016343.4	c.162+284A>G		intron_variant		ENST00000366955.8	NP_057427.3
CENPF	XM_011509082.4	c.162+284A>G		intron_variant			XP_011507384.1
CENPF	XM_017000086.3	c.162+284A>G		intron_variant			XP_016855575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8	c.162+284A>G		intron_variant		1	NM_016343.4	ENSP00000355922	P2
CENPF	ENST00000706765.1	c.162+284A>G		intron_variant				ENSP00000516538	A2
CENPF	ENST00000464322.5	n.330+284A>G		intron_variant, non_coding_transcript_variant		2
CENPF	ENST00000706764.1	n.340+284A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10465 AN: 149574 Hom.: 424 Cov.: 31

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0514

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0540

Gnomad OTH AF: 0.0647

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

GnomAD4 genome AF: 0.0701 AC: 10491 AN: 149688 Hom.: 424 Cov.: 31 AF XY: 0.0713 AC XY: 5193 AN XY: 72832

Gnomad4 AFR AF: 0.0829

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0514

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0227

Gnomad4 NFE AF: 0.0540

Gnomad4 OTH AF: 0.0654

Alfa AF: 0.0661 Hom.: 144

Bravo AF: 0.0777

Asia WGS AF: 0.123 AC: 425 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.89
CADD	Benign	0.99
DANN	Benign	0.56

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: rs17023274; hg19: chr1-214787543;