16-57469418-C-A

Variant names:

• chr16-57469418-C-A
• rs2161647
• NM_032940.3:c.387+125C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032940.3. 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
	POLR2C	NM_032940.3	MANE Select	c.387+125C>A		intron	N/A	NP_116558.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR2C	ENST00000219252.10	TSL:1 MANE Select	c.387+125C>A		intron	N/A	ENSP00000219252.4
	POLR2C	ENST00000880578.1		c.318+125C>A		intron	N/A	ENSP00000550637.1
	POLR2C	ENST00000563115.5	TSL:2	n.577C>A		non_coding_transcript_exon	Exon 5 of 5

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

GnomAD2 exomes AF: 0.0484 AC: 8699 AN: 179824 AF XY: 0.0478

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

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: 94 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

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

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: 33 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: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0340 AC: 2314 AN: 68018

Other (OTH) AF: 0.0743 AC: 157 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
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)

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

Other links and lift over

dbSNP: rs2161647; hg19: chr16-57503330;