chr15-90966212-C-A

Variant names:

• chr15-90966212-C-A
• rs15172
• NM_003981.4:c.*919G>T

Variant summary

Our verdict is Benign. The variant received -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]

ENSG00000284946 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.006).
• 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 rank	MANE	Protein	UniProt
PRC1	NM_003981.4	c.*919G>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000394249.8	NP_003972.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRC1	ENST00000394249	c.*919G>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_003981.4	ENSP00000377793.3
ENSG00000284946	ENST00000643536.1	n.*4544G>T		non_coding_transcript_exon_variant	Exon 35 of 35			ENSP00000494429.1
ENSG00000284946	ENST00000643536.1	n.*4544G>T		3_prime_UTR_variant	Exon 35 of 35			ENSP00000494429.1

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 AC: 209 AN: 1404

Gnomad4 AMR exome AF: 0.0128 AC: 34 AN: 2646

Gnomad4 ASJ exome AF: 0.0270 AC: 28 AN: 1036

Gnomad4 EAS exome AF: 0.00135 AC: 3 AN: 2228

Gnomad4 SAS exome AF: 0.00459 AC: 28 AN: 6102

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 2324

Gnomad4 NFE exome AF: 0.00145 AC: 37 AN: 25446

Gnomad4 Remaining exome AF: 0.00948 AC: 24 AN: 2532

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 AC: 0.167285 AN: 0.167285

Gnomad4 AMR AF: 0.0213 AC: 0.0213183 AN: 0.0213183

Gnomad4 ASJ AF: 0.0285 AC: 0.0285303 AN: 0.0285303

Gnomad4 EAS AF: 0.00116 AC: 0.00115785 AN: 0.00115785

Gnomad4 SAS AF: 0.00601 AC: 0.0060141 AN: 0.0060141

Gnomad4 FIN AF: 0.0000944 AC: 0.0000944465 AN: 0.0000944465

Gnomad4 NFE AF: 0.00201 AC: 0.00201411 AN: 0.00201411

Gnomad4 OTH AF: 0.0436 AC: 0.0435606 AN: 0.0435606

Alfa AF: 0.0279 Hom.: 157

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

Feb 01, 2014

Research Lab, National Institute of Public Health

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

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
Mutation Taster		=100/0	polymorphism (auto)

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;