rs10494983

Positions:

• chr1-214648166-G-T

Variant summary

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

The NM_016343.4(CENPF):​c.7831-509G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 152,136 control chromosomes in the GnomAD database, including 513 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 0.074 (513 hom., cov: 32)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPF	NM_016343.4	c.7831-509G>T		intron_variant		ENST00000366955.8	NP_057427.3
CENPF	XM_017000086.3	c.7831-509G>T		intron_variant			XP_016855575.1
CENPF	XM_011509082.4	c.7831-509G>T		intron_variant			XP_011507384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8	c.7831-509G>T		intron_variant		1	NM_016343.4	ENSP00000355922.3
CENPF	ENST00000706765.1	c.7831-509G>T		intron_variant				ENSP00000516538.1

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11185 AN: 152018 Hom.: 511 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0694

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

GnomAD4 genome AF: 0.0738 AC: 11223 AN: 152136 Hom.: 513 Cov.: 32 AF XY: 0.0743 AC XY: 5527 AN XY: 74380

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0521

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0216

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0646 Hom.: 48

Bravo AF: 0.0825

Asia WGS AF: 0.118 AC: 410 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.67

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: rs10494983; hg19: chr1-214821509;