rs6843

Positions:

• chr19-1088286-T-C

Variant summary

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

The NM_002695.5(POLR2E):​c.*449A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,196 control chromosomes in the GnomAD database, including 46,368 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 0.78 (46332 hom., cov: 32)
  • Exomes 𝑓: 0.74 (36 hom.)
• Consequence: POLR2E NM_002695.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

Genes affected

POLR2E (HGNC:9192): (RNA polymerase II, I and III subunit E) This gene encodes the fifth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA-directed RNA polymerases and is present in two-fold molar excess over the other polymerase subunits. An interaction between this subunit and a hepatitis virus transactivating protein has been demonstrated, suggesting that interaction between transcriptional activators and the polymerase can occur through this subunit. A pseudogene is located on chromosome 11. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

POLR2E (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR2E	NM_002695.5	c.*449A>G		3_prime_UTR_variant	8/8	ENST00000615234.5	NP_002686.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR2E	ENST00000615234	c.*449A>G		3_prime_UTR_variant	8/8	1	NM_002695.5	ENSP00000478303.1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118025 AN: 151948 Hom.: 46294 Cov.: 32

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.763

GnomAD4 exome AF: 0.742 AC: 95 AN: 128 Hom.: 36 Cov.: 0 AF XY: 0.743 AC XY: 55 AN XY: 74

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.760

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.438

GnomAD4 genome AF: 0.777 AC: 118113 AN: 152068 Hom.: 46332 Cov.: 32 AF XY: 0.773 AC XY: 57482 AN XY: 74336

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.803

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.754

Alfa AF: 0.759 Hom.: 52103

Bravo AF: 0.785

Asia WGS AF: 0.623 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.30
DANN	Benign	0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6843; hg19: chr19-1088285;