rs10494984

Positions:

• chr1-214648337-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016343.4(CENPF):​c.7831-338G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 393,866 control chromosomes in the GnomAD database, including 893 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.050 (259 hom., cov: 32)
  • Exomes 𝑓: 0.058 (634 hom.)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPF	NM_016343.4	c.7831-338G>C		intron_variant		ENST00000366955.8
CENPF	XM_011509082.4	c.7831-338G>C		intron_variant
CENPF	XM_017000086.3	c.7831-338G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPF	ENST00000366955.8	c.7831-338G>C		intron_variant		1	NM_016343.4	P2
CENPF	ENST00000706765.1	c.7831-338G>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.0503 AC: 7654 AN: 152128 Hom.: 259 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0366

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.0581 AC: 14042 AN: 241620 Hom.: 634 AF XY: 0.0627 AC XY: 8429 AN XY: 134474

Gnomad4 AFR exome AF: 0.0502

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.0462

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0208

Gnomad4 NFE exome AF: 0.0353

Gnomad4 OTH exome AF: 0.0493

GnomAD4 genome AF: 0.0504 AC: 7676 AN: 152246 Hom.: 259 Cov.: 32 AF XY: 0.0511 AC XY: 3804 AN XY: 74444

Gnomad4 AFR AF: 0.0510

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0171

Gnomad4 NFE AF: 0.0366

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0442 Hom.: 20

Bravo AF: 0.0587

Asia WGS AF: 0.103 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.73

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: rs10494984; hg19: chr1-214821680;