Variant 17-7496000-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_000937.5(POLR2A):c.153C>T(p.Arg51=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,613,896 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 19 hom., cov: 32)

Exomes 𝑓: 0.017 ( 255 hom. )

Consequence

POLR2A
NM_000937.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

POLR2A (HGNC:9187): (RNA polymerase II subunit A) This gene encodes the largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a carboxy terminal domain composed of heptapeptide repeats that are essential for polymerase activity. These repeats contain serine and threonine residues that are phosphorylated in actively transcribing RNA polymerase. In addition, this subunit, in combination with several other polymerase subunits, forms the DNA binding domain of the polymerase, a groove in which the DNA template is transcribed into RNA. [provided by RefSeq, Jul 2008]

POLR2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 17-7496000-C-T is Benign according to our data. Variant chr17-7496000-C-T is described in ClinVar as [Benign]. Clinvar id is 3059166.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.73 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0125 (1898/152306) while in subpopulation NFE AF= 0.0197 (1341/68022). AF 95% confidence interval is 0.0188. There are 19 homozygotes in gnomad4. There are 830 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1898 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR2A	NM_000937.5 linkuse as main transcript	c.153C>T	p.Arg51=	synonymous_variant	2/30	ENST00000643490.2	NP_000928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	Appris
POLR2A	ENST00000674977.2 linkuse as main transcript	c.153C>T	p.Arg51=	synonymous_variant	2/30		ENSP00000502190	P1
POLR2A	ENST00000572844.1 linkuse as main transcript	n.298C>T		non_coding_transcript_exon_variant	2/10	1
POLR2A	ENST00000617998.6 linkuse as main transcript	n.552C>T		non_coding_transcript_exon_variant	2/29	1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1898

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00384

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.00688

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0137

AC:

3431

AN:

250648

Hom.:

AF XY:

0.0141

AC XY:

1908

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.00344

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00536

Gnomad FIN exome

AF:

0.00818

Gnomad NFE exome

AF:

0.0216

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.0174

AC:

25396

AN:

1461590

Hom.:

255

Cov.:

AF XY:

0.0172

AC XY:

12492

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00236

Gnomad4 AMR exome

AF:

0.0118

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00602

Gnomad4 FIN exome

AF:

0.00921

Gnomad4 NFE exome

AF:

0.0201

Gnomad4 OTH exome

AF:

0.0173

GnomAD4 genome

AF:

0.0125

AC:

1898

AN:

152306

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

830

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00382

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00688

Gnomad4 NFE

AF:

0.0197

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0171

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0228

EpiControl

AF:

0.0237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

POLR2A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.5

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over