1-214613402-C-A

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.-41-312C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0062 in 194,732 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (16 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (0 hom.)
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.180

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]

UBE2V1P13 (HGNC:52411): (UBE2V1 pseudogene 13)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 1-214613402-C-A is Benign according to our data. Variant chr1-214613402-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1198092.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00774 (1178/152132) while in subpopulation AFR AF= 0.0272 (1127/41480). AF 95% confidence interval is 0.0259. There are 16 homozygotes in gnomad4. There are 554 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPF	NM_016343.4	c.-41-312C>A		intron_variant		ENST00000366955.8
CENPF	XM_017000086.3	c.-219C>A		5_prime_UTR_variant	1/20
CENPF	XM_011509082.4	c.-41-312C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPF	ENST00000366955.8	c.-41-312C>A		intron_variant		1	NM_016343.4	P2
UBE2V1P13	ENST00000436983.2			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00770 AC: 1171 AN: 152014 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000681 AC: 29 AN: 42600 Hom.: 0 Cov.: 0 AF XY: 0.000957 AC XY: 22 AN XY: 22996

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000113

Gnomad4 OTH exome AF: 0.00164

GnomAD4 genome AF: 0.00774 AC: 1178 AN: 152132 Hom.: 16 Cov.: 32 AF XY: 0.00745 AC XY: 554 AN XY: 74352

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.00249

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00350 Hom.: 1

Bravo AF: 0.00822

Asia WGS AF: 0.00115 AC: 4 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

Jul 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	1.5
Dann	Benign	0.68

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: rs115736692; hg19: chr1-214786745;