rs484416

Positions:

• chr1-10431152-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_199294.3(CENPS):​c.51+584G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 1,445,608 control chromosomes in the GnomAD database, including 6,170 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 0.11 (1099 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5071 hom.)
• Consequence: CENPS NM_199294.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592

Genes affected

CENPS (HGNC:23163): (centromere protein S) This gene was identified in the neuroblastoma tumor suppressor candidate region on chromosome 1p36. It contains a TFIID-31 domain, similar to that found in TATA box-binding protein-associated factor, TAF(II)31, which is required for p53-mediated transcription activation. This gene was expressed at very low levels in neuroblastoma tumors, and was shown to reduce cell growth in neuroblastoma cells, suggesting that it may have a role in a cell death pathway. The protein is a component of multiple complexes, including the Fanconi anemia (FA) core complex, the APITD1/CENPS complex, and the CENPA-CAD (nucleosome distal) complex. Known functions include an involvement with chromatin associations of the FA core complex, and a role in the stable assembly of the outer kinetochore. Alternative splicing of this gene results in multiple transcript variants. Naturally occurring read-through transcripts also exist between this gene and the downstream cortistatin (CORT) gene, as represented in GeneID:100526739. An APITD1-related pseudogene has been identified on chromosome 7. [provided by RefSeq, Nov 2010]

CENPS-CORT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPS	NM_199294.3	c.51+584G>A		intron_variant		ENST00000309048.8
CENPS-CORT	NR_037187.2	n.403G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPS	ENST00000309048.8	c.51+584G>A		intron_variant		1	NM_199294.3	P1
CENPS	ENST00000462462.1	c.-138G>A		5_prime_UTR_variant	1/3	3
CENPS	ENST00000477755.1	c.-138G>A		5_prime_UTR_variant, NMD_transcript_variant	1/5	2
CENPS	ENST00000602486.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16673 AN: 152088 Hom.: 1095 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.0848

GnomAD4 exome AF: 0.0815 AC: 105466 AN: 1293402 Hom.: 5071 Cov.: 31 AF XY: 0.0826 AC XY: 51976 AN XY: 629628

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.0715

Gnomad4 OTH exome AF: 0.0834

GnomAD4 genome AF: 0.110 AC: 16698 AN: 152206 Hom.: 1099 Cov.: 32 AF XY: 0.114 AC XY: 8506 AN XY: 74416

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0693

Gnomad4 OTH AF: 0.0872

Alfa AF: 0.0806 Hom.: 116

Bravo AF: 0.112

Asia WGS AF: 0.183 AC: 633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.1
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.56		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.56		Position offset: 32

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

Publications

LitVar

Other links and lift over

dbSNP: rs484416; hg19: chr1-10491209;