1-10431152-G-A

Position:

• chr1-10431152-G-A

Variant summary

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

The NM_001243768.2(CENPS-CORT):​c.-138G>A variant causes a 5 prime UTR 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-CORT NM_001243768.2 5_prime_UTR
• 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:38843): (CENPS-CORT readthrough) This locus represents naturally occurring read-through transcription between the neighboring APITD1 (apoptosis-inducing, TAF9-like domain 1) and CORT (cortistatin) genes. Alternative splicing results in multiple transcript variants, two of which encode fusion proteins that share sequence identity with the products of each individual gene. [provided by RefSeq, Aug 2011]

CENPS (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	Protein	UniProt
CENPS	NM_199294.3	c.51+584G>A		intron_variant		ENST00000309048.8	NP_954988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CENPS	ENST00000309048.8	c.51+584G>A		intron_variant		1	NM_199294.3	ENSP00000308583.2
CENPS-CORT	ENST00000602787.6	c.51+584G>A		intron_variant		3		ENSP00000473509.2

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;