chr15-90966212-C-A

Position:

• chr15-90966212-C-A

Variant summary

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

The NM_003981.4(PRC1):​c.*919G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 196,124 control chromosomes in the GnomAD database, including 611 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 0.050 (592 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (19 hom.)
• Consequence: PRC1 NM_003981.4 3_prime_UTR
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.561

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRC1	NM_003981.4	c.*919G>T		3_prime_UTR_variant	15/15	ENST00000394249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRC1	ENST00000394249.8	c.*919G>T		3_prime_UTR_variant	15/15	1	NM_003981.4
PRC1	ENST00000361188.9	c.*919G>T		3_prime_UTR_variant	14/14	1		P1
PRC1	ENST00000556972.6	c.*425G>T		3_prime_UTR_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7620 AN: 152084 Hom.: 588 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.0440

GnomAD4 exome AF: 0.00840 AC: 369 AN: 43922 Hom.: 19 Cov.: 0 AF XY: 0.00782 AC XY: 180 AN XY: 23004

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.0128

Gnomad4 ASJ exome AF: 0.0270

Gnomad4 EAS exome AF: 0.00135

Gnomad4 SAS exome AF: 0.00459

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00145

Gnomad4 OTH exome AF: 0.00948

GnomAD4 genome AF: 0.0502 AC: 7646 AN: 152202 Hom.: 592 Cov.: 32 AF XY: 0.0481 AC XY: 3575 AN XY: 74390

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.0213

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00201

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0280 Hom.: 101

Bravo AF: 0.0575

Asia WGS AF: 0.0120 AC: 42 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	-0.89
CADD	Benign	6.7
DANN	Benign	0.79
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: rs15172; hg19: chr15-91509442;