1-214613971-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016343.4(CENPF):c.162+55G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000593 in 1,469,444 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.697

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-214613971-G-C is Benign according to our data. Variant chr1-214613971-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1197904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0034 (517/152264) while in subpopulation AFR AF= 0.0118 (489/41530). AF 95% confidence interval is 0.0109. There are 7 homozygotes in gnomad4. There are 244 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPF	NM_016343.4	c.162+55G>C		intron_variant		ENST00000366955.8
CENPF	XM_011509082.4	c.162+55G>C		intron_variant
CENPF	XM_017000086.3	c.162+55G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPF	ENST00000366955.8	c.162+55G>C		intron_variant		1	NM_016343.4	P2
CENPF	ENST00000706765.1	c.162+55G>C		intron_variant				A2
CENPF	ENST00000464322.5	n.330+55G>C		intron_variant, non_coding_transcript_variant		2
CENPF	ENST00000706764.1	n.340+55G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00339 AC: 516 AN: 152146 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000269 AC: 354 AN: 1317180 Hom.: 0 AF XY: 0.000239 AC XY: 156 AN XY: 654068

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.000849

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000286

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.000476

GnomAD4 genome AF: 0.00340 AC: 517 AN: 152264 Hom.: 7 Cov.: 32 AF XY: 0.00328 AC XY: 244 AN XY: 74442

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00214 Hom.: 0

Bravo AF: 0.00396

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.46
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs113840975; hg19: chr1-214787314;