rs14280

Variant names:

• chr15-90966504-A-G
• rs14280
• NM_003981.4:c.*627T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate 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
• Publications: 14 publications found

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.025).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003981.4. 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
	PRC1	NM_003981.4	MANE Select	c.*627T>C		3_prime_UTR	Exon 15 of 15	NP_003972.2	O43663-1
	PRC1	NM_199413.3		c.*627T>C		3_prime_UTR	Exon 14 of 14	NP_955445.2	O43663-4
	PRC1	NM_001267580.2		c.*670T>C		3_prime_UTR	Exon 13 of 13	NP_001254509.2	O43663-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRC1	ENST00000394249.8	TSL:1 MANE Select	c.*627T>C		3_prime_UTR	Exon 15 of 15	ENSP00000377793.3	O43663-1
	PRC1	ENST00000361188.9	TSL:1	c.*627T>C		3_prime_UTR	Exon 14 of 14	ENSP00000354679.5	O43663-4
	ENSG00000284946	ENST00000643536.1		n.*4252T>C		non_coding_transcript_exon	Exon 35 of 35	ENSP00000494429.1	A0A2R8YDQ0

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

African (AFR) AF: 0.0789 AC: 671 AN: 8504

American (AMR) AF: 0.0476 AC: 1286 AN: 27038

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 1416 AN: 10526

East Asian (EAS) AF: 0.0208 AC: 188 AN: 9052

South Asian (SAS) AF: 0.104 AC: 6181 AN: 59270

European-Finnish (FIN) AF: 0.0720 AC: 909 AN: 12628

Middle Eastern (MID) AF: 0.106 AC: 291 AN: 2752

European-Non Finnish (NFE) AF: 0.0850 AC: 13227 AN: 155584

Other (OTH) AF: 0.0888 AC: 1245 AN: 14018

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

African (AFR) AF: 0.0807 AC: 3354 AN: 41556

American (AMR) AF: 0.0645 AC: 986 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3472

East Asian (EAS) AF: 0.0210 AC: 109 AN: 5192

South Asian (SAS) AF: 0.100 AC: 483 AN: 4816

European-Finnish (FIN) AF: 0.0580 AC: 616 AN: 10622

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0855 AC: 5818 AN: 68012

Other (OTH) AF: 0.0914 AC: 193 AN: 2112

Alfa AF: 0.0787 Hom.: 117

Bravo AF: 0.0790

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Familial cancer of breast (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.0
DANN	Benign	0.84
PhyloP100		-0.35
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

Other links and lift over

dbSNP: rs14280; hg19: chr15-91509734;