15-90966504-A-G

Variant summary

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

The NM_003981.4(PRC1):c.*627T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 451,644 control chromosomes in the GnomAD database, including 1,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.080 (539 hom., cov: 32)
  • Exomes 𝑓: 0.085 (1266 hom.)
• Consequence: PRC1 NM_003981.4 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.355

Genes affected

PRC1 (HGNC:9341): (protein regulator of cytokinesis 1) This gene encodes a protein that is involved in cytokinesis. The protein is present at high levels during the S and G2/M phases of mitosis but its levels drop dramatically when the cell exits mitosis and enters the G1 phase. It is located in the nucleus during interphase, becomes associated with mitotic spindles in a highly dynamic manner during mitosis, and localizes to the cell mid-body during cytokinesis. This protein has been shown to be a substrate of several cyclin-dependent kinases (CDKs). It is necessary for polarizing parallel microtubules and concentrating the factors responsible for contractile ring assembly. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

PRC1-AS1 (HGNC:48587): (PRC1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRC1	NM_003981.4	c.*627T>C		3_prime_UTR_variant	15/15	ENST00000394249.8
PRC1-AS1	NR_051984.1	n.136A>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRC1	ENST00000394249.8	c.*627T>C		3_prime_UTR_variant	15/15	1	NM_003981.4
PRC1-AS1	ENST00000554388.2	n.165A>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12219 AN: 152154 Hom.: 541 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0646

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0209

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.0580

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.0923

GnomAD4 exome AF: 0.0849 AC: 25414 AN: 299372 Hom.: 1266 Cov.: 0 AF XY: 0.0873 AC XY: 14868 AN XY: 170352

Gnomad4 AFR exome AF: 0.0789

Gnomad4 AMR exome AF: 0.0476

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.0208

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0720

Gnomad4 NFE exome AF: 0.0850

Gnomad4 OTH exome AF: 0.0888

GnomAD4 genome AF: 0.0803 AC: 12231 AN: 152272 Hom.: 539 Cov.: 32 AF XY: 0.0800 AC XY: 5956 AN XY: 74468

Gnomad4 AFR AF: 0.0807

Gnomad4 AMR AF: 0.0645

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0210

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0580

Gnomad4 NFE AF: 0.0855

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0787 Hom.: 116

Bravo AF: 0.0790

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial cancer of breast Uncertain:1

Uncertain significance, no assertion criteria provided

research

Research Lab, National Institute of Public Health

Feb 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	3.0
Dann	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs14280; hg19: chr15-91509734;