rs2290203

Positions:

• chr15-90968837-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003981.4(PRC1):​c.1791+242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,314,436 control chromosomes in the GnomAD database, including 37,985 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (7172 hom., cov: 32)
  • Exomes 𝑓: 0.22 (30813 hom.)
• Consequence: PRC1 NM_003981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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]

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

ACMG classification

Verdict is Benign. Variant got -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 = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRC1	NM_003981.4	c.1791+242C>T		intron_variant		ENST00000394249.8
PRC1-AS1	NR_051984.1	n.310+2159G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRC1	ENST00000394249.8	c.1791+242C>T		intron_variant		1	NM_003981.4
PRC1-AS1	ENST00000554388.2	n.339+2159G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44001 AN: 151968 Hom.: 7147 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.220 AC: 255818 AN: 1162350 Hom.: 30813 Cov.: 31 AF XY: 0.222 AC XY: 123931 AN XY: 558882

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.290 AC: 44065 AN: 152086 Hom.: 7172 Cov.: 32 AF XY: 0.292 AC XY: 21728 AN XY: 74360

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.305

Alfa AF: 0.220 Hom.: 4298

Bravo AF: 0.302

Asia WGS AF: 0.466 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.44

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: rs2290203; hg19: chr15-91512067;