rs2161647

Positions:

• chr16-57469418-C-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
POLR2C	NM_032940.3	c.387+125C>A		intron_variant		ENST00000219252.10	NP_116558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR2C	ENST00000219252.10	c.387+125C>A		intron_variant		1	NM_032940.3	ENSP00000219252.4

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11402 AN: 152152 Hom.: 746 Cov.: 32

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

GnomAD3 exomes AF: 0.0484 AC: 8699 AN: 179824 Hom.: 353 AF XY: 0.0478 AC XY: 4669 AN XY: 97592

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 SAS exome AF: 0.0676

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.: 12 AF XY: 0.0431 AC XY: 20611 AN XY: 478472

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.0354

Gnomad4 ASJ exome AF: 0.0661

Gnomad4 EAS exome AF: 0.00264

Gnomad4 SAS exome AF: 0.0677

Gnomad4 FIN exome AF: 0.0188

Gnomad4 NFE exome AF: 0.0370

Gnomad4 OTH exome AF: 0.0555

GnomAD4 genome AF: 0.0750 AC: 11421 AN: 152270 Hom.: 748 Cov.: 32 AF XY: 0.0737 AC XY: 5489 AN XY: 74456

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.00636

Gnomad4 SAS AF: 0.0721

Gnomad4 FIN AF: 0.0217

Gnomad4 NFE AF: 0.0340

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0597 Hom.: 136

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	11
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2161647; hg19: chr16-57503330;