1-214613457-T-C

Position:

• chr1-214613457-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000366955.8(CENPF):​c.-41-257T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.051 in 222,294 control chromosomes in the GnomAD database, including 420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (235 hom., cov: 32)
  • Exomes 𝑓: 0.058 (185 hom.)
• Consequence: CENPF ENST00000366955.8 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.400

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-214613457-T-C is Benign according to our data. Variant chr1-214613457-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1209451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPF	NM_016343.4	c.-41-257T>C		intron_variant		ENST00000366955.8	NP_057427.3
CENPF	XM_017000086.3	c.-164T>C		5_prime_UTR_variant	1/20		XP_016855575.1
CENPF	XM_011509082.4	c.-41-257T>C		intron_variant			XP_011507384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8	c.-41-257T>C		intron_variant		1	NM_016343.4	ENSP00000355922	P2

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 7218 AN: 151896 Hom.: 235 Cov.: 32

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0965

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0170

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0507

GnomAD4 exome AF: 0.0584 AC: 4103 AN: 70280 Hom.: 185 AF XY: 0.0616 AC XY: 2200 AN XY: 35698

Gnomad4 AFR exome AF: 0.0346

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.0568

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0251

Gnomad4 NFE exome AF: 0.0457

Gnomad4 OTH exome AF: 0.0640

GnomAD4 genome AF: 0.0476 AC: 7236 AN: 152014 Hom.: 235 Cov.: 32 AF XY: 0.0489 AC XY: 3633 AN XY: 74318

Gnomad4 AFR AF: 0.0340

Gnomad4 AMR AF: 0.0969

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0170

Gnomad4 NFE AF: 0.0404

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0436 Hom.: 21

Bravo AF: 0.0555

Asia WGS AF: 0.109 AC: 377 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 31, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	10
DANN	Benign	0.74

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: rs12405890; hg19: chr1-214786800;