rs8042680

Positions:

• chr15-90978107-C-A
• chr15-90978107-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.1107+1051G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,136 control chromosomes in the GnomAD database, including 27,206 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 0.54 (27206 hom., cov: 31)
• Consequence: PRC1 NM_003981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRC1	NM_003981.4	c.1107+1051G>T		intron_variant		ENST00000394249.8	NP_003972.2
PRC1-AS1	NR_051984.1	n.311-3848C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRC1	ENST00000394249.8	c.1107+1051G>T		intron_variant		1	NM_003981.4	ENSP00000377793
PRC1-AS1	ENST00000554388.2	n.340-3848C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82147 AN: 152018 Hom.: 27137 Cov.: 31

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.541 AC: 82282 AN: 152136 Hom.: 27206 Cov.: 31 AF XY: 0.548 AC XY: 40738 AN XY: 74364

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.550

Alfa AF: 0.383 Hom.: 30241

Bravo AF: 0.580

Asia WGS AF: 0.845 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.79
DANN	Benign	0.31

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: rs8042680; hg19: chr15-91521337;