rs10494983

Variant names:

• chr1-214648166-G-T
• rs10494983
• NM_016343.4:c.7831-509G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

CENPF Gene-Disease associations (from GenCC):

• Stromme syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Illumina, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CENPF	NM_016343.4	c.7831-509G>T		intron_variant	Intron 13 of 19	ENST00000366955.8	NP_057427.3
CENPF	XM_017000086.3	c.7831-509G>T		intron_variant	Intron 13 of 19		XP_016855575.1
CENPF	XM_011509082.4	c.7831-509G>T		intron_variant	Intron 13 of 18		XP_011507384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8	c.7831-509G>T		intron_variant	Intron 13 of 19	1	NM_016343.4	ENSP00000355922.3
CENPF	ENST00000706765.1	c.7831-509G>T		intron_variant	Intron 13 of 18			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

African (AFR) AF: 0.104 AC: 4326 AN: 41506

American (AMR) AF: 0.108 AC: 1648 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0521 AC: 181 AN: 3472

East Asian (EAS) AF: 0.111 AC: 573 AN: 5164

South Asian (SAS) AF: 0.138 AC: 667 AN: 4816

European-Finnish (FIN) AF: 0.0216 AC: 229 AN: 10596

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0500 AC: 3397 AN: 67984

Other (OTH) AF: 0.0705 AC: 149 AN: 2112

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
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10494983; hg19: chr1-214821509;