15-90980483-C-G

Position:

• chr15-90980483-C-G

Variant summary

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

The NM_003981.4(PRC1):​c.823-94G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,168,748 control chromosomes in the GnomAD database, including 39,259 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 0.31 (9185 hom., cov: 29)
  • Exomes 𝑓: 0.23 (30074 hom.)
• Consequence: PRC1 NM_003981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRC1	NM_003981.4	c.823-94G>C		intron_variant		ENST00000394249.8	NP_003972.2
PRC1-AS1	NR_051984.1	n.311-1472C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRC1	ENST00000394249.8	c.823-94G>C		intron_variant		1	NM_003981.4	ENSP00000377793
PRC1-AS1	ENST00000554388.2	n.340-1472C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 46275 AN: 148850 Hom.: 9147 Cov.: 29

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.232 AC: 236250 AN: 1019806 Hom.: 30074 Cov.: 15 AF XY: 0.232 AC XY: 119188 AN XY: 513058

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.364

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.518

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.311 AC: 46367 AN: 148942 Hom.: 9185 Cov.: 29 AF XY: 0.315 AC XY: 22798 AN XY: 72476

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.325

Alfa AF: 0.242 Hom.: 705

Bravo AF: 0.332

Asia WGS AF: 0.439 AC: 1523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.59

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: rs1867226; hg19: chr15-91523713;