rs5967249

Positions:

• chrX-101130607-G-C

Variant summary

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

The NM_001386188.2(CENPI):​c.1287+534G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 111,773 control chromosomes in the GnomAD database, including 3,523 homozygotes. There are 8,808 hemizygotes in GnomAD. 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 0.27 (3523 hom., 8808 hem., cov: 23)
• Consequence: CENPI NM_001386188.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

Genes affected

CENPI (HGNC:3968): (centromere protein I) This gene encodes a centromere protein that is a component of the CENPA-NAC (nucleosome-associated) complex. This complex is critical for accurate chromosome alignment and segregation and it ensures proper mitotic progression. This protein regulates the recruitment of kinetochore-associated proteins that are required to generate the spindle checkpoint signal. The product of this gene is involved in the response of gonadal tissues to follicle-stimulating hormone. Mutations in this gene may be involved in human X-linked disorders of gonadal development and gametogenesis. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 13. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CENPI	NM_001386188.2	c.1287+534G>C		intron_variant		ENST00000682095.1	NP_001373117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPI	ENST00000682095.1	c.1287+534G>C		intron_variant			NM_001386188.2	ENSP00000507927.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 30301 AN: 111719 Hom.: 3523 Cov.: 23 AF XY: 0.259 AC XY: 8782 AN XY: 33961

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.271 AC: 30325 AN: 111773 Hom.: 3523 Cov.: 23 AF XY: 0.259 AC XY: 8808 AN XY: 34025

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.255

Alfa AF: 0.243 Hom.: 1481

Bravo AF: 0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.4
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs5967249; hg19: chrX-100385596;