Genetic Variant PRC1:c.823-94G>C (chr15-90980483-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.341

Publications

20 publications found

Variant links:

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 links:

ENSG00000284946 (HGNC:):

ENSG00000284946 links:

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

PRC1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRC1	NM_003981.4 link	c.823-94G>C		intron_variant	Intron 6 of 14	ENST00000394249.8	NP_003972.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRC1	ENST00000394249.8 link	c.823-94G>C		intron_variant	Intron 6 of 14	1	NM_003981.4	ENSP00000377793.3
ENSG00000284946	ENST00000643536.1 link	n.*786-94G>C		intron_variant	Intron 27 of 34			ENSP00000494429.1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

46275

AN:

148850

Hom.:

9147

Cov.:

show subpopulations

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.:

AF XY:

0.232

AC XY:

119188

AN XY:

513058

show subpopulations

African (AFR)

AF:

0.575

AC:

14193

AN:

24682

American (AMR)

AF:

0.364

AC:

9280

AN:

25492

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

4734

AN:

17660

East Asian (EAS)

AF:

0.518

AC:

18983

AN:

36626

South Asian (SAS)

AF:

0.318

AC:

19254

AN:

60592

European-Finnish (FIN)

AF:

0.193

AC:

6979

AN:

36228

Middle Eastern (MID)

AF:

0.288

AC:

1278

AN:

4440

European-Non Finnish (NFE)

AF:

0.195

AC:

149789

AN:

769014

Other (OTH)

AF:

0.261

AC:

11760

AN:

45072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

7753

15506

23260

31013

38766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5410

10820

16230

21640

27050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.311

AC:

46367

AN:

148942

Hom.:

9185

Cov.:

AF XY:

0.315

AC XY:

22798

AN XY:

72476

show subpopulations

African (AFR)

AF:

0.541

AC:

21795

AN:

40252

American (AMR)

AF:

0.319

AC:

4738

AN:

14840

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

860

AN:

3448

East Asian (EAS)

AF:

0.523

AC:

2661

AN:

5088

South Asian (SAS)

AF:

0.313

AC:

1472

AN:

4708

European-Finnish (FIN)

AF:

0.192

AC:

1882

AN:

9824

Middle Eastern (MID)

AF:

0.325

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.177

AC:

11959

AN:

67518

Other (OTH)

AF:

0.325

AC:

675

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

1385

2770

4155

5540

6925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.59

PhyloP100

0.34

PromoterAI

-0.0085

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over