1-214648337-G-C

Variant names:

• chr1-214648337-G-C
• rs10494984
• NM_016343.4:c.7831-338G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016343.4(CENPF):​c.7831-338G>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
• Publications: 0 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=-0.86).
• 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 rank	MANE	Protein	UniProt
CENPF	NM_016343.4	c.7831-338G>C		intron_variant	Intron 13 of 19	ENST00000366955.8	NP_057427.3
CENPF	XM_017000086.3	c.7831-338G>C		intron_variant	Intron 13 of 19		XP_016855575.1
CENPF	XM_011509082.4	c.7831-338G>C		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.7831-338G>C		intron_variant	Intron 13 of 19	1	NM_016343.4	ENSP00000355922.3
CENPF	ENST00000706765.1	c.7831-338G>C		intron_variant	Intron 13 of 18			ENSP00000516538.1

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

African (AFR) AF: 0.0502 AC: 347 AN: 6916

American (AMR) AF: 0.130 AC: 1600 AN: 12268

Ashkenazi Jewish (ASJ) AF: 0.0462 AC: 272 AN: 5892

East Asian (EAS) AF: 0.121 AC: 1361 AN: 11272

South Asian (SAS) AF: 0.108 AC: 4764 AN: 44178

European-Finnish (FIN) AF: 0.0208 AC: 233 AN: 11226

Middle Eastern (MID) AF: 0.0462 AC: 38 AN: 822

European-Non Finnish (NFE) AF: 0.0353 AC: 4845 AN: 137238

Other (OTH) AF: 0.0493 AC: 582 AN: 11808

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

African (AFR) AF: 0.0510 AC: 2117 AN: 41544

American (AMR) AF: 0.0970 AC: 1483 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3468

East Asian (EAS) AF: 0.111 AC: 574 AN: 5178

South Asian (SAS) AF: 0.105 AC: 505 AN: 4824

European-Finnish (FIN) AF: 0.0171 AC: 181 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0366 AC: 2489 AN: 68014

Other (OTH) AF: 0.0539 AC: 114 AN: 2114

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
PhyloP100		-0.57
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: rs10494984; hg19: chr1-214821680;