rs2070064

Variant names:

• chr1-214613787-G-A
• rs2070064
• NM_016343.4:c.33G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-214613787-G-A
• chr1-214613787-G-C
• chr1-214613787-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_016343.4(CENPF):​c.33G>A​(p.Gly11Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,607,980 control chromosomes in the GnomAD database, including 189,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G11G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.36 (12687 hom., cov: 32)
  • Exomes 𝑓: 0.48 (176929 hom.)
• Consequence: CENPF NM_016343.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.213
• Publications: 20 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 1-214613787-G-A is Benign according to our data. Variant chr1-214613787-G-A is described in ClinVar as Benign. ClinVar VariationId is 1209807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.213 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 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.33G>A	p.Gly11Gly	synonymous	Exon 2 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.33G>A	p.Gly11Gly	synonymous	Exon 2 of 20	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.33G>A	p.Gly11Gly	synonymous	Exon 2 of 21	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.33G>A	p.Gly11Gly	synonymous	Exon 2 of 20	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55368 AN: 151948 Hom.: 12688 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.382

GnomAD2 exomes AF: 0.397 AC: 97610 AN: 245878 AF XY: 0.409

Gnomad AFR exome AF: 0.0981

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.494

Gnomad EAS exome AF: 0.117

Gnomad FIN exome AF: 0.463

Gnomad NFE exome AF: 0.520

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.480 AC: 698572 AN: 1455914 Hom.: 176929 Cov.: 36 AF XY: 0.477 AC XY: 345750 AN XY: 724178

African (AFR) AF: 0.0906 AC: 2996 AN: 33066

American (AMR) AF: 0.269 AC: 11709 AN: 43600

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 12803 AN: 25952

East Asian (EAS) AF: 0.130 AC: 5144 AN: 39436

South Asian (SAS) AF: 0.326 AC: 27788 AN: 85144

European-Finnish (FIN) AF: 0.459 AC: 24472 AN: 53338

Middle Eastern (MID) AF: 0.400 AC: 2299 AN: 5742

European-Non Finnish (NFE) AF: 0.527 AC: 584568 AN: 1109508

Other (OTH) AF: 0.446 AC: 26793 AN: 60128

GnomAD4 genome AF: 0.364 AC: 55368 AN: 152066 Hom.: 12687 Cov.: 32 AF XY: 0.359 AC XY: 26663 AN XY: 74314

African (AFR) AF: 0.109 AC: 4505 AN: 41498

American (AMR) AF: 0.329 AC: 5026 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1720 AN: 3470

East Asian (EAS) AF: 0.118 AC: 613 AN: 5176

South Asian (SAS) AF: 0.309 AC: 1485 AN: 4812

European-Finnish (FIN) AF: 0.459 AC: 4845 AN: 10554

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35756 AN: 67968

Other (OTH) AF: 0.382 AC: 805 AN: 2106

Alfa AF: 0.452 Hom.: 16577

Bravo AF: 0.342

Asia WGS AF: 0.197 AC: 689 AN: 3478

EpiCase AF: 0.521

EpiControl AF: 0.510

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	-0.41
CADD	Benign	8.9
DANN	Benign	0.83
PhyloP100		-0.21
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Mutation Taster		=99/1	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: rs2070064; hg19: chr1-214787130; COSMIC: COSV65273614; COSMIC: COSV65273614;