Variant chr2-112547573-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019014.6(POLR1B):c.492+6G>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,612,890 control chromosomes in the GnomAD database, including 265,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23239 hom., cov: 31)

Exomes 𝑓: 0.57 ( 242056 hom. )

Consequence

POLR1B
NM_019014.6 splice_donor_region, intron

Scores

Splicing: ADA: 0.0002779

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.636

Variant links:

Genes affected

POLR1B (HGNC:20454): (RNA polymerase I subunit B) Eukaryotic RNA polymerase I (pol I) is responsible for the transcription of ribosomal RNA (rRNA) genes and production of rRNA, the primary component of ribosomes. Pol I is a multisubunit enzyme composed of 6 to 14 polypeptides, depending on the species. Most of the mass of the pol I complex derives from the 2 largest subunits, Rpa1 and Rpa2 in yeast. POLR1B is homologous to Rpa2 (Seither and Grummt, 1996 [PubMed 8921381]).[supplied by OMIM, Mar 2008]

POLR1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-112547573-G-C is Benign according to our data. Variant chr2-112547573-G-C is described in ClinVar as [Benign]. Clinvar id is 1233209.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1B	NM_019014.6 linkuse as main transcript	c.492+6G>C		splice_donor_region_variant, intron_variant		ENST00000263331.10	NP_061887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1B	ENST00000263331.10 linkuse as main transcript	c.492+6G>C		splice_donor_region_variant, intron_variant		2	NM_019014.6	ENSP00000263331	P1	Q9H9Y6-1

Frequencies

GnomAD3 genomes

AF:

0.549

AC:

83420

AN:

151816

Hom.:

23220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.521

Gnomad ASJ

AF:

0.632

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.586

GnomAD3 exomes

AF:

0.537

AC:

134718

AN:

250680

Hom.:

37182

AF XY:

0.542

AC XY:

73430

AN XY:

135520

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.476

Gnomad ASJ exome

AF:

0.630

Gnomad EAS exome

AF:

0.350

Gnomad SAS exome

AF:

0.505

Gnomad FIN exome

AF:

0.493

Gnomad NFE exome

AF:

0.595

Gnomad OTH exome

AF:

0.570

GnomAD4 exome

AF:

0.572

AC:

836173

AN:

1460956

Hom.:

242056

Cov.:

AF XY:

0.572

AC XY:

415486

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.535

Gnomad4 AMR exome

AF:

0.483

Gnomad4 ASJ exome

AF:

0.627

Gnomad4 EAS exome

AF:

0.340

Gnomad4 SAS exome

AF:

0.508

Gnomad4 FIN exome

AF:

0.489

Gnomad4 NFE exome

AF:

0.593

Gnomad4 OTH exome

AF:

0.563

GnomAD4 genome

AF:

0.549

AC:

83479

AN:

151934

Hom.:

23239

Cov.:

AF XY:

0.542

AC XY:

40247

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.527

Gnomad4 AMR

AF:

0.521

Gnomad4 ASJ

AF:

0.632

Gnomad4 EAS

AF:

0.360

Gnomad4 SAS

AF:

0.501

Gnomad4 FIN

AF:

0.487

Gnomad4 NFE

AF:

0.592

Gnomad4 OTH

AF:

0.588

Alfa

AF:

0.579

Hom.:

8142

Bravo

AF:

0.551

Asia WGS

AF:

0.465

AC:

1616

AN:

3478

EpiCase

AF:

0.596

EpiControl

AF:

0.609

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.14

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.038

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