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GeneBe

19-1093977-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002695.5(POLR2E):c.159G>A(p.Pro53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00555 in 1,613,710 control chromosomes in the GnomAD database, including 452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 222 hom., cov: 32)
Exomes 𝑓: 0.0030 ( 230 hom. )

Consequence

POLR2E
NM_002695.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.50
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-1093977-C-T is Benign according to our data. Variant chr19-1093977-C-T is described in ClinVar as [Benign]. Clinvar id is 768946.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.5 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
POLR2ENM_002695.5 linkuse as main transcriptc.159G>A p.Pro53= synonymous_variant 2/8 ENST00000615234.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
POLR2EENST00000615234.5 linkuse as main transcriptc.159G>A p.Pro53= synonymous_variant 2/81 NM_002695.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0299
AC:
4555
AN:
152192
Hom.:
222
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.104
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0110
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.0210
GnomAD3 exomes
AF:
0.00766
AC:
1913
AN:
249878
Hom.:
101
AF XY:
0.00551
AC XY:
746
AN XY:
135444
show subpopulations
Gnomad AFR exome
AF:
0.108
Gnomad AMR exome
AF:
0.00342
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000981
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000284
Gnomad OTH exome
AF:
0.00394
GnomAD4 exome
AF:
0.00301
AC:
4400
AN:
1461400
Hom.:
230
Cov.:
30
AF XY:
0.00262
AC XY:
1903
AN XY:
727018
show subpopulations
Gnomad4 AFR exome
AF:
0.110
Gnomad4 AMR exome
AF:
0.00448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000148
Gnomad4 OTH exome
AF:
0.00571
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0299
AC:
4559
AN:
152310
Hom.:
222
Cov.:
32
AF XY:
0.0285
AC XY:
2122
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.104
Gnomad4 AMR
AF:
0.0109
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.0213
Alfa
AF:
0.0139
Hom.:
48
Bravo
AF:
0.0350
Asia WGS
AF:
0.00491
AC:
17
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
0.32
Dann
Benign
0.94
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs75657655; hg19: chr19-1093976; API