rs484416

Variant names:

• chr1-10431152-G-A
• rs484416
• NM_199294.3:c.51+584G>A

Variant summary

Our verdict is Benign. The variant received -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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CENPS	NM_199294.3	c.51+584G>A		intron_variant	Intron 1 of 4	ENST00000309048.8	NP_954988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPS	ENST00000309048.8	c.51+584G>A		intron_variant	Intron 1 of 4	1	NM_199294.3	ENSP00000308583.2
CENPS-CORT	ENST00000602787.6	c.51+584G>A		intron_variant	Intron 1 of 5	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 AC: 4547 AN: 28602

Gnomad4 AMR exome AF: 0.178 AC: 3949 AN: 22246

Gnomad4 ASJ exome AF: 0.0150 AC: 292 AN: 19472

Gnomad4 EAS exome AF: 0.162 AC: 5609 AN: 34608

Gnomad4 SAS exome AF: 0.133 AC: 8542 AN: 64458

Gnomad4 FIN exome AF: 0.127 AC: 3798 AN: 29876

Gnomad4 NFE exome AF: 0.0715 AC: 74137 AN: 1036714

Gnomad4 Remaining exome AF: 0.0834 AC: 4485 AN: 53780

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 AC: 0.157762 AN: 0.157762

Gnomad4 AMR AF: 0.137 AC: 0.136988 AN: 0.136988

Gnomad4 ASJ AF: 0.0207 AC: 0.0207373 AN: 0.0207373

Gnomad4 EAS AF: 0.157 AC: 0.156745 AN: 0.156745

Gnomad4 SAS AF: 0.141 AC: 0.140547 AN: 0.140547

Gnomad4 FIN AF: 0.145 AC: 0.144501 AN: 0.144501

Gnomad4 NFE AF: 0.0693 AC: 0.0693305 AN: 0.0693305

Gnomad4 OTH AF: 0.0872 AC: 0.0872038 AN: 0.0872038

Alfa AF: 0.0849 Hom.: 343

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
Mutation Taster		=100/0	polymorphism (auto)

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;