1-214613402-C-A

Variant names:

• chr1-214613402-C-A
• rs115736692
• NM_016343.4:c.-41-312C>A

Variant summary

Our verdict is Benign. The variant received -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
• 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

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.-41-312C>A		intron	N/A	NP_057427.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPF	ENST00000366955.8	TSL:1 MANE Select	c.-41-312C>A		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.-41-312C>A		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.-41-312C>A		intron	N/A	ENSP00000605042.1

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

African (AFR) AF: 0.0151 AC: 20 AN: 1322

American (AMR) AF: 0.00136 AC: 2 AN: 1470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1018

East Asian (EAS) AF: 0.00 AC: 0 AN: 1382

South Asian (SAS) AF: 0.00 AC: 0 AN: 5000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 160

European-Non Finnish (NFE) AF: 0.000113 AC: 3 AN: 26602

Other (OTH) AF: 0.00164 AC: 4 AN: 2442

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

African (AFR) AF: 0.0272 AC: 1127 AN: 41480

American (AMR) AF: 0.00249 AC: 38 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68014

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00333 Hom.: 1

Bravo AF: 0.00822

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

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: rs115736692; hg19: chr1-214786745;