dbSNP rs2161647: POLR2C:c.387+125C>A (chr16-57469418-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032940.3(POLR2C):c.387+125C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 1,076,962 control chromosomes in the GnomAD database, including 2,003 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 0.075 ( 748 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1255 hom. )

Consequence

POLR2C
NM_032940.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

Publications

3 publications found

Variant links:

Genes affected

POLR2C (HGNC:9189): (RNA polymerase II subunit C) This gene encodes the third largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a cysteine rich region and exists as a heterodimer with another polymerase subunit, POLR2J. These two subunits form a core subassembly unit of the polymerase. A pseudogene has been identified on chromosome 21. [provided by RefSeq, Jul 2008]

POLR2C 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=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR2C	NM_032940.3 link	c.387+125C>A		intron_variant	Intron 5 of 8	ENST00000219252.10	NP_116558.1	P19387Q6FGR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR2C	ENST00000219252.10 link	c.387+125C>A		intron_variant	Intron 5 of 8	1	NM_032940.3	ENSP00000219252.4		P19387

Frequencies

GnomAD3 genomes

AF:

0.0749

AC:

11402

AN:

152152

Hom.:

746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0516

Gnomad ASJ

AF:

0.0628

Gnomad EAS

AF:

0.00635

Gnomad SAS

AF:

0.0720

Gnomad FIN

AF:

0.0217

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0340

Gnomad OTH

AF:

0.0751

GnomAD2 exomes

AF:

0.0484

AC:

8699

AN:

179824

AF XY:

0.0478

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.0334

Gnomad ASJ exome

AF:

0.0691

Gnomad EAS exome

AF:

0.00606

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.0385

Gnomad OTH exome

AF:

0.0502

GnomAD4 exome

AF:

0.0423

AC:

39129

AN:

924692

Hom.:

1255

Cov.:

AF XY:

0.0431

AC XY:

20611

AN XY:

478472

show subpopulations

African (AFR)

AF:

0.180

AC:

4172

AN:

23142

American (AMR)

AF:

0.0354

AC:

1350

AN:

38136

Ashkenazi Jewish (ASJ)

AF:

0.0661

AC:

1451

AN:

21954

East Asian (EAS)

AF:

0.00264

AC:

AN:

35602

South Asian (SAS)

AF:

0.0677

AC:

4892

AN:

72240

European-Finnish (FIN)

AF:

0.0188

AC:

879

AN:

46716

Middle Eastern (MID)

AF:

0.0570

AC:

272

AN:

4772

European-Non Finnish (NFE)

AF:

0.0370

AC:

23652

AN:

639506

Other (OTH)

AF:

0.0555

AC:

2367

AN:

42624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2056

4112

6168

8224

10280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

772

1544

2316

3088

3860

<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:

0.0750

AC:

11421

AN:

152270

Hom.:

748

Cov.:

AF XY:

0.0737

AC XY:

5489

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.176

AC:

7310

AN:

41538

American (AMR)

AF:

0.0515

AC:

787

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0628

AC:

218

AN:

3472

East Asian (EAS)

AF:

0.00636

AC:

AN:

5186

South Asian (SAS)

AF:

0.0721

AC:

348

AN:

4826

European-Finnish (FIN)

AF:

0.0217

AC:

230

AN:

10616

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0340

AC:

2314

AN:

68018

Other (OTH)

AF:

0.0743

AC:

157

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

527

1054

1582

2109

2636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0617

Hom.:

147

Bravo

AF:

0.0808

Asia WGS

AF:

0.0560

AC:

195

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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