15-90971530-C-T

Variant names:

• chr15-90971530-C-T
• rs11852999
• NM_003981.4:c.1462-1016G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003981.4(PRC1):​c.1462-1016G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,794 control chromosomes in the GnomAD database, including 1,552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.11 (1552 hom., cov: 31)
• Consequence: PRC1 NM_003981.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.281
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 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.1462-1016G>A		intron	N/A	NP_003972.2	O43663-1
	PRC1	NM_199413.3		c.1462-1016G>A		intron	N/A	NP_955445.2	O43663-4
	PRC1	NM_001267580.2		c.1339-1016G>A		intron	N/A	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.1462-1016G>A		intron	N/A	ENSP00000377793.3	O43663-1
	PRC1	ENST00000361188.9	TSL:1	c.1462-1016G>A		intron	N/A	ENSP00000354679.5	O43663-4
	ENSG00000284946	ENST00000643536.1		n.*1425-1016G>A		intron	N/A	ENSP00000494429.1	A0A2R8YDQ0

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16859 AN: 151684 Hom.: 1551 Cov.: 31

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0826

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16861 AN: 151794 Hom.: 1552 Cov.: 31 AF XY: 0.117 AC XY: 8691 AN XY: 74160

African (AFR) AF: 0.0780 AC: 3225 AN: 41362

American (AMR) AF: 0.244 AC: 3711 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.0826 AC: 286 AN: 3464

East Asian (EAS) AF: 0.469 AC: 2415 AN: 5148

South Asian (SAS) AF: 0.199 AC: 955 AN: 4806

European-Finnish (FIN) AF: 0.0726 AC: 763 AN: 10510

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.0759 AC: 5158 AN: 67966

Other (OTH) AF: 0.125 AC: 264 AN: 2106

Alfa AF: 0.106 Hom.: 538

Bravo AF: 0.124

Asia WGS AF: 0.295 AC: 1023 AN: 3476

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Breast carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.64
PhyloP100		0.28
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: rs11852999; hg19: chr15-91514760;