Variant 17-7495924-CCTTT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_000937.5(POLR2A):c.94-8_94-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 1,613,604 control chromosomes in the GnomAD database, including 1,788 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.059 ( 410 hom., cov: 31)

Exomes 𝑓: 0.038 ( 1378 hom. )

Consequence

POLR2A
NM_000937.5 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.417

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 17-7495924-CCTTT-C is Benign according to our data. Variant chr17-7495924-CCTTT-C is described in ClinVar as [Benign]. Clinvar id is 3056317.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR2A	NM_000937.5 linkuse as main transcript	c.94-8_94-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000643490.2	NP_000928.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	Appris
POLR2A	ENST00000674977.2 linkuse as main transcript	c.94-8_94-5del	splice_polypyrimidine_tract_variant, intron_variant		ENSP00000502190	P1
POLR2A	ENST00000572844.1 linkuse as main transcript	n.239-8_239-5del	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
POLR2A	ENST00000617998.6 linkuse as main transcript	n.493-8_493-5del	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.0591

AC:

8988

AN:

152102

Hom.:

396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0314

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.0584

Gnomad SAS

AF:

0.0131

Gnomad FIN

AF:

0.0286

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0355

Gnomad OTH

AF:

0.0450

GnomAD3 exomes

AF:

0.0361

AC:

9082

AN:

251270

Hom.:

276

AF XY:

0.0341

AC XY:

4628

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.0185

Gnomad ASJ exome

AF:

0.0439

Gnomad EAS exome

AF:

0.0567

Gnomad SAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.0268

Gnomad NFE exome

AF:

0.0324

Gnomad OTH exome

AF:

0.0331

GnomAD4 exome

AF:

0.0378

AC:

55244

AN:

1461384

Hom.:

1378

AF XY:

0.0366

AC XY:

26633

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.0206

Gnomad4 ASJ exome

AF:

0.0466

Gnomad4 EAS exome

AF:

0.0713

Gnomad4 SAS exome

AF:

0.0132

Gnomad4 FIN exome

AF:

0.0259

Gnomad4 NFE exome

AF:

0.0364

Gnomad4 OTH exome

AF:

0.0447

GnomAD4 genome

AF:

0.0593

AC:

9028

AN:

152220

Hom.:

410

Cov.:

AF XY:

0.0574

AC XY:

4270

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.0314

Gnomad4 ASJ

AF:

0.0461

Gnomad4 EAS

AF:

0.0582

Gnomad4 SAS

AF:

0.0127

Gnomad4 FIN

AF:

0.0286

Gnomad4 NFE

AF:

0.0355

Gnomad4 OTH

AF:

0.0455

Alfa

AF:

0.0470

Hom.:

Bravo

AF:

0.0628

Asia WGS

AF:

0.0450

AC:

155

AN:

3478

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

Dec 05, 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

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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