rs3790648

Variant names:

• chr1-214647151-G-A
• rs3790648
• NM_016343.4:c.7581G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016343.4(CENPF):​c.7581G>A​(p.Leu2527Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 1,613,690 control chromosomes in the GnomAD database, including 4,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (511 hom., cov: 33)
  • Exomes 𝑓: 0.062 (3715 hom.)
• Consequence: CENPF NM_016343.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.518
• Publications: 11 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: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, G2P, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-214647151-G-A is Benign according to our data. Variant chr1-214647151-G-A is described in ClinVar as Benign. ClinVar VariationId is 1209680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.518 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPF	NM_016343.4	MANE Select	c.7581G>A	p.Leu2527Leu	synonymous	Exon 13 of 20	NP_057427.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPF	ENST00000366955.8	TSL:1 MANE Select	c.7581G>A	p.Leu2527Leu	synonymous	Exon 13 of 20	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.7701G>A	p.Leu2567Leu	synonymous	Exon 14 of 21	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.7581G>A	p.Leu2527Leu	synonymous	Exon 13 of 20	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11208 AN: 152144 Hom.: 509 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0697

GnomAD2 exomes AF: 0.0833 AC: 20856 AN: 250344 AF XY: 0.0820

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.0542

Gnomad EAS exome AF: 0.125

Gnomad FIN exome AF: 0.0252

Gnomad NFE exome AF: 0.0489

Gnomad OTH exome AF: 0.0650

GnomAD4 exome AF: 0.0622 AC: 90950 AN: 1461430 Hom.: 3715 Cov.: 34 AF XY: 0.0640 AC XY: 46564 AN XY: 727020

African (AFR) AF: 0.108 AC: 3598 AN: 33468

American (AMR) AF: 0.148 AC: 6630 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0517 AC: 1351 AN: 26124

East Asian (EAS) AF: 0.115 AC: 4581 AN: 39668

South Asian (SAS) AF: 0.148 AC: 12750 AN: 86212

European-Finnish (FIN) AF: 0.0267 AC: 1427 AN: 53404

Middle Eastern (MID) AF: 0.0732 AC: 422 AN: 5764

European-Non Finnish (NFE) AF: 0.0505 AC: 56174 AN: 1111714

Other (OTH) AF: 0.0665 AC: 4017 AN: 60378

GnomAD4 genome AF: 0.0739 AC: 11246 AN: 152260 Hom.: 511 Cov.: 33 AF XY: 0.0744 AC XY: 5538 AN XY: 74432

African (AFR) AF: 0.104 AC: 4329 AN: 41554

American (AMR) AF: 0.108 AC: 1646 AN: 15294

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

East Asian (EAS) AF: 0.111 AC: 573 AN: 5178

South Asian (SAS) AF: 0.142 AC: 683 AN: 4818

European-Finnish (FIN) AF: 0.0218 AC: 231 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0500 AC: 3400 AN: 68018

Other (OTH) AF: 0.0709 AC: 150 AN: 2116

Alfa AF: 0.0603 Hom.: 523

Bravo AF: 0.0825

Asia WGS AF: 0.119 AC: 413 AN: 3478

EpiCase AF: 0.0506

EpiControl AF: 0.0522

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Stromme syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.12
DANN	Benign	0.57
PhyloP100		-0.52
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: rs3790648; hg19: chr1-214820494; COSMIC: COSV65277749; COSMIC: COSV65277749;