NM_016343.4:c.7831-338G>A

Variant names:

• chr1-214648337-G-A
• rs10494984
• NM_016343.4:c.7831-338G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016343.4(CENPF):​c.7831-338G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• 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]

CENPF Gene-Disease associations (from GenCC):

• Stromme syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Illumina, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPF	NM_016343.4	c.7831-338G>A		intron_variant	Intron 13 of 19	ENST00000366955.8	NP_057427.3
CENPF	XM_017000086.3	c.7831-338G>A		intron_variant	Intron 13 of 19		XP_016855575.1
CENPF	XM_011509082.4	c.7831-338G>A		intron_variant	Intron 13 of 18		XP_011507384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8	c.7831-338G>A		intron_variant	Intron 13 of 19	1	NM_016343.4	ENSP00000355922.3
CENPF	ENST00000706765.1	c.7831-338G>A		intron_variant	Intron 13 of 18			ENSP00000516538.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 241706 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134514

African (AFR) AF: 0.00 AC: 0 AN: 6916

American (AMR) AF: 0.00 AC: 0 AN: 12286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5892

East Asian (EAS) AF: 0.00 AC: 0 AN: 11278

South Asian (SAS) AF: 0.00 AC: 0 AN: 44206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 822

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 137264

Other (OTH) AF: 0.00 AC: 0 AN: 11814

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.6
DANN	Benign	0.85
PhyloP100		-0.57

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: rs10494984; hg19: chr1-214821680;