rs6496742

Variant names:

• chr15-90979806-C-T
• rs6496742
• NM_003981.4:c.970+436G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003981.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRC1	NM_003981.4	MANE Select	c.970+436G>A		intron	N/A	NP_003972.2	O43663-1
	PRC1	NM_199413.3		c.970+436G>A		intron	N/A	NP_955445.2	O43663-4
	PRC1	NM_001267580.2		c.847+436G>A		intron	N/A	NP_001254509.2	O43663-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRC1	ENST00000394249.8	TSL:1 MANE Select	c.970+436G>A		intron	N/A	ENSP00000377793.3	O43663-1
	PRC1	ENST00000361188.9	TSL:1	c.970+436G>A		intron	N/A	ENSP00000354679.5	O43663-4
	ENSG00000284946	ENST00000643536.1		n.*933+436G>A		intron	N/A	ENSP00000494429.1	A0A2R8YDQ0

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

African (AFR) AF: 0.655 AC: 27139 AN: 41420

American (AMR) AF: 0.364 AC: 5560 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1127 AN: 3470

East Asian (EAS) AF: 0.521 AC: 2698 AN: 5176

South Asian (SAS) AF: 0.459 AC: 2218 AN: 4828

European-Finnish (FIN) AF: 0.260 AC: 2758 AN: 10590

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16862 AN: 67964

Other (OTH) AF: 0.399 AC: 842 AN: 2112

Alfa AF: 0.358 Hom.: 8385

Bravo AF: 0.413

Asia WGS AF: 0.540 AC: 1874 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Familial cancer of breast (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		-0.36
PromoterAI		-0.028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6496742; hg19: chr15-91523036;