rs10520699

Variant names:

• chr15-90979736-G-A
• rs10520699
• NM_003981.4:c.971-442C>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.971-442C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 152,206 control chromosomes in the GnomAD database, including 742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.085 (742 hom., cov: 32)
• Consequence: PRC1 NM_003981.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.592
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRC1	NM_003981.4	c.971-442C>T		intron_variant	Intron 7 of 14	ENST00000394249.8	NP_003972.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRC1	ENST00000394249.8	c.971-442C>T		intron_variant	Intron 7 of 14	1	NM_003981.4	ENSP00000377793.3
ENSG00000284946	ENST00000643536.1	n.*934-442C>T		intron_variant	Intron 28 of 34			ENSP00000494429.1

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12876 AN: 152088 Hom.: 742 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0672

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0163

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.0778

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

GnomAD4 genome AF: 0.0846 AC: 12870 AN: 152206 Hom.: 742 Cov.: 32 AF XY: 0.0837 AC XY: 6224 AN XY: 74404

African (AFR) AF: 0.0268 AC: 1112 AN: 41538

American (AMR) AF: 0.0670 AC: 1024 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 167 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0162 AC: 78 AN: 4828

European-Finnish (FIN) AF: 0.156 AC: 1651 AN: 10582

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8568 AN: 68006

Other (OTH) AF: 0.0770 AC: 163 AN: 2116

Alfa AF: 0.0979 Hom.: 733

Bravo AF: 0.0773

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Breast carcinoma Other:1

Feb 01, 2014

Research Lab, National Institute of Public Health

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.65
DANN	Benign	0.54
PhyloP100		-0.59
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: rs10520699; hg19: chr15-91522966;