rs6496742

chr15-90979806-C-T

Variant summary

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

The NM_003981.4(PRC1):c.970+436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,016 control chromosomes in the GnomAD database, including 14,141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.39 (14141 hom., cov: 32)
• Consequence: PRC1 NM_003981.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.358

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRC1	NM_003981.4	c.970+436G>A		intron_variant		ENST00000394249.8
PRC1-AS1	NR_051984.1	n.311-2149C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRC1	ENST00000394249.8	c.970+436G>A		intron_variant		1	NM_003981.4
PRC1-AS1	ENST00000554388.2	n.340-2149C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59549 AN: 151898 Hom.: 14094 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.392 AC: 59655 AN: 152016 Hom.: 14141 Cov.: 32 AF XY: 0.394 AC XY: 29275 AN XY: 74314

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.399

Alfa AF: 0.302 Hom.: 2027

Bravo AF: 0.413

Asia WGS AF: 0.540 AC: 1874 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial cancer of breast Uncertain:1

Uncertain significance, no assertion criteria provided

research

Research Lab, National Institute of Public Health

Feb 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.3
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs6496742; hg19: chr15-91523036;