rs484416

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 7 publications found

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 -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243768.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPS	NM_199294.3	MANE Select	c.51+584G>A		intron	N/A	NP_954988.1	Q8N2Z9-1
	CENPS-CORT	NM_001243768.2		c.-138G>A		5_prime_UTR	Exon 1 of 4	NP_001230697.1	A0A087WT10
	CENPS-CORT	NM_198544.4		c.51+584G>A		intron	N/A	NP_940946.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPS	ENST00000309048.8	TSL:1 MANE Select	c.51+584G>A		intron	N/A	ENSP00000308583.2	Q8N2Z9-1
	CENPS-CORT	ENST00000602787.6	TSL:3	c.51+584G>A		intron	N/A	ENSP00000473509.2
	CENPS-CORT	ENST00000602296.6	TSL:3	c.-138G>A		5_prime_UTR	Exon 1 of 4	ENSP00000473401.2	A0A087WT10

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

African (AFR) AF: 0.159 AC: 4547 AN: 28602

American (AMR) AF: 0.178 AC: 3949 AN: 22246

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 292 AN: 19472

East Asian (EAS) AF: 0.162 AC: 5609 AN: 34608

South Asian (SAS) AF: 0.133 AC: 8542 AN: 64458

European-Finnish (FIN) AF: 0.127 AC: 3798 AN: 29876

Middle Eastern (MID) AF: 0.0293 AC: 107 AN: 3646

European-Non Finnish (NFE) AF: 0.0715 AC: 74137 AN: 1036714

Other (OTH) 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

African (AFR) AF: 0.158 AC: 6549 AN: 41512

American (AMR) AF: 0.137 AC: 2094 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3472

East Asian (EAS) AF: 0.157 AC: 811 AN: 5174

South Asian (SAS) AF: 0.141 AC: 678 AN: 4824

European-Finnish (FIN) AF: 0.145 AC: 1532 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0693 AC: 4716 AN: 68022

Other (OTH) AF: 0.0872 AC: 184 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.1
DANN	Benign	0.86
PhyloP100		0.59
PromoterAI		-0.013	Neutral
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

Other links and lift over

dbSNP: rs484416; hg19: chr1-10491209;