15-90966362-T-C

Variant summary

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

The NM_003981.4(PRC1):c.*769A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 319,920 control chromosomes in the GnomAD database, including 36,268 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 0.47 (20288 hom., cov: 32)
  • Exomes 𝑓: 0.40 (15980 hom.)
• Consequence: PRC1 NM_003981.4 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.844

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRC1	NM_003981.4	c.*769A>G		3_prime_UTR_variant	15/15	ENST00000394249.8
PRC1-AS1	NR_051984.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRC1	ENST00000394249.8	c.*769A>G		3_prime_UTR_variant	15/15	1	NM_003981.4
PRC1-AS1	ENST00000554388.2	n.23T>C		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71632 AN: 151886 Hom.: 20238 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.397 AC: 66604 AN: 167916 Hom.: 15980 Cov.: 0 AF XY: 0.409 AC XY: 37934 AN XY: 92754

Gnomad4 AFR exome AF: 0.712

Gnomad4 AMR exome AF: 0.646

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.995

Gnomad4 SAS exome AF: 0.495

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.384

GnomAD4 genome AF: 0.472 AC: 71749 AN: 152004 Hom.: 20288 Cov.: 32 AF XY: 0.479 AC XY: 35616 AN XY: 74316

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.988

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.491

Alfa AF: 0.348 Hom.: 15530

Bravo AF: 0.508

Asia WGS AF: 0.749 AC: 2600 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	-0.86
Cadd	Benign	3.7
Dann	Benign	0.59
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: rs7601; hg19: chr15-91509592;