rs1048194

Positions:

• chr16-81031097-G-A
• chr16-81031097-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100624.3(CENPN):​c.*2446G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 151,530 control chromosomes in the GnomAD database, including 498 homozygotes. 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: 𝑓 0.080 (498 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CENPN NM_001100624.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239

Genes affected

CENPN (HGNC:30873): (centromere protein N) The protein encoded by this gene forms part of the nucleosome-associated complex and is important for kinetochore assembly. It is bound to kinetochores during S phase and G2 and recruits other proteins to the centromere. Pseudogenes of this gene are located on chromosome 2. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ENSG00000284512 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPN	NM_001100624.3	c.*2446G>A		3_prime_UTR_variant	11/11	ENST00000305850.10	NP_001094094.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPN	ENST00000305850.10	c.*2446G>A		3_prime_UTR_variant	11/11	1	NM_001100624.3	ENSP00000305608.5
ENSG00000284512	ENST00000640345.1	c.*2+3658C>T		intron_variant		5		ENSP00000492798.1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12087 AN: 151412 Hom.: 495 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0262

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.0670

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0799 AC: 12105 AN: 151530 Hom.: 498 Cov.: 32 AF XY: 0.0785 AC XY: 5813 AN XY: 74010

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0254

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0768

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0549 Hom.: 78

Bravo AF: 0.0771

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1048194; hg19: chr16-81064702;