chr15-90974249-G-A

Variant names:

• chr15-90974249-G-A
• rs17636091
• NM_003981.4:c.1351-3C>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.1351-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 1,609,786 control chromosomes in the GnomAD database, including 13,909 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.10 (1465 hom., cov: 32)
  • Exomes 𝑓: 0.099 (12444 hom.)
• Consequence: PRC1 NM_003981.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002213
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.60
• Publications: 20 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRC1	NM_003981.4	MANE Select	c.1351-3C>T		splice_region intron	N/A	NP_003972.2
	PRC1	NM_199413.3		c.1351-3C>T		splice_region intron	N/A	NP_955445.2
	PRC1	NM_001267580.2		c.1228-3C>T		splice_region intron	N/A	NP_001254509.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRC1	ENST00000394249.8	TSL:1 MANE Select	c.1351-3C>T		splice_region intron	N/A	ENSP00000377793.3
	PRC1	ENST00000361188.9	TSL:1	c.1351-3C>T		splice_region intron	N/A	ENSP00000354679.5
	ENSG00000284946	ENST00000643536.1		n.*1314-3C>T		splice_region intron	N/A	ENSP00000494429.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15671 AN: 152176 Hom.: 1464 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0729

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.151 AC: 38012 AN: 251280 AF XY: 0.146

Gnomad AFR exome AF: 0.0479

Gnomad AMR exome AF: 0.319

Gnomad ASJ exome AF: 0.0723

Gnomad EAS exome AF: 0.470

Gnomad FIN exome AF: 0.0743

Gnomad NFE exome AF: 0.0746

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.0995 AC: 145004 AN: 1457492 Hom.: 12444 Cov.: 30 AF XY: 0.101 AC XY: 73366 AN XY: 725356

African (AFR) AF: 0.0454 AC: 1516 AN: 33364

American (AMR) AF: 0.309 AC: 13818 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 1898 AN: 26114

East Asian (EAS) AF: 0.488 AC: 19384 AN: 39688

South Asian (SAS) AF: 0.185 AC: 15961 AN: 86154

European-Finnish (FIN) AF: 0.0757 AC: 4036 AN: 53350

Middle Eastern (MID) AF: 0.155 AC: 890 AN: 5732

European-Non Finnish (NFE) AF: 0.0728 AC: 80660 AN: 1108122

Other (OTH) AF: 0.114 AC: 6841 AN: 60266

GnomAD4 genome AF: 0.103 AC: 15671 AN: 152294 Hom.: 1465 Cov.: 32 AF XY: 0.109 AC XY: 8139 AN XY: 74456

African (AFR) AF: 0.0492 AC: 2047 AN: 41576

American (AMR) AF: 0.242 AC: 3695 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3472

East Asian (EAS) AF: 0.465 AC: 2406 AN: 5170

South Asian (SAS) AF: 0.199 AC: 961 AN: 4822

European-Finnish (FIN) AF: 0.0729 AC: 774 AN: 10624

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0760 AC: 5170 AN: 68022

Other (OTH) AF: 0.121 AC: 256 AN: 2112

Alfa AF: 0.0954 Hom.: 807

Bravo AF: 0.115

Asia WGS AF: 0.293 AC: 1017 AN: 3478

EpiCase AF: 0.0838

EpiControl AF: 0.0896

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	-0.58
CADD	Benign	4.7
DANN	Benign	0.79
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00022
dbscSNV1_RF	Benign	0.076
SpliceAI score (max)		0.010		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: rs17636091; hg19: chr15-91517479; COSMIC: COSV62695460; COSMIC: COSV62695460;