Variant 2-112542706-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_019014.6(POLR1B):c.177+35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,605,832 control chromosomes in the GnomAD database, including 11,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1999 hom., cov: 32)

Exomes 𝑓: 0.10 ( 9316 hom. )

Consequence

POLR1B
NM_019014.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.698

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 -14 ACMG points.

BP4

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

BP6

Variant 2-112542706-C-G is Benign according to our data. Variant chr2-112542706-C-G is described in ClinVar as [Benign]. Clinvar id is 1261814.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1B	NM_019014.6 linkuse as main transcript	c.177+35C>G		intron_variant		ENST00000263331.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1B	ENST00000263331.10 linkuse as main transcript	c.177+35C>G		intron_variant		2	NM_019014.6	P1	Q9H9Y6-1

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21534

AN:

152072

Hom.:

1993

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.0789

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.0796

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0761

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.138

AC:

31331

AN:

227740

Hom.:

2919

AF XY:

0.129

AC XY:

16185

AN XY:

125196

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.0819

Gnomad EAS exome

AF:

0.344

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.0755

Gnomad NFE exome

AF:

0.0776

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.100

AC:

145739

AN:

1453642

Hom.:

9316

Cov.:

AF XY:

0.0998

AC XY:

72099

AN XY:

722638

show subpopulations

Gnomad4 AFR exome

AF:

0.229

Gnomad4 AMR exome

AF:

0.222

Gnomad4 ASJ exome

AF:

0.0833

Gnomad4 EAS exome

AF:

0.323

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.0770

Gnomad4 NFE exome

AF:

0.0819

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.142

AC:

21563

AN:

152190

Hom.:

1999

Cov.:

AF XY:

0.143

AC XY:

10620

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.234

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.0789

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.0796

Gnomad4 NFE

AF:

0.0761

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.0567

Hom.:

Bravo

AF:

0.157

Asia WGS

AF:

0.239

AC:

831

AN:

3478

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 submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.7

DANN

Benign

0.71

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