Variant chr2-112549250-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_019014.6(POLR1B):c.493-17A>G 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 0.109 in 1,610,540 control chromosomes in the GnomAD database, including 12,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2095 hom., cov: 31)

Exomes 𝑓: 0.11 ( 10092 hom. )

Consequence

POLR1B
NM_019014.6 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.377

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 -16 ACMG points.

BP6

Variant 2-112549250-A-G is Benign according to our data. Variant chr2-112549250-A-G is described in ClinVar as [Benign]. Clinvar id is 1220927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
POLR1B	NM_019014.6 linkuse as main transcript	c.493-17A>G		splice_polypyrimidine_tract_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.493-17A>G		splice_polypyrimidine_tract_variant, intron_variant		2	NM_019014.6	ENSP00000263331	P1	Q9H9Y6-1

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22407

AN:

151878

Hom.:

2089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.0824

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.0854

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0836

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.139

AC:

34802

AN:

250102

Hom.:

3330

AF XY:

0.132

AC XY:

17792

AN XY:

135300

show subpopulations

Gnomad AFR exome

AF:

0.238

Gnomad AMR exome

AF:

0.232

Gnomad ASJ exome

AF:

0.0833

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.0816

Gnomad NFE exome

AF:

0.0830

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.105

AC:

153191

AN:

1458544

Hom.:

10092

Cov.:

AF XY:

0.104

AC XY:

75829

AN XY:

725778

show subpopulations

Gnomad4 AFR exome

AF:

0.235

Gnomad4 AMR exome

AF:

0.225

Gnomad4 ASJ exome

AF:

0.0858

Gnomad4 EAS exome

AF:

0.322

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.0825

Gnomad4 NFE exome

AF:

0.0873

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.148

AC:

22438

AN:

151996

Hom.:

2095

Cov.:

AF XY:

0.149

AC XY:

11052

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.239

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.0824

Gnomad4 EAS

AF:

0.320

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.0854

Gnomad4 NFE

AF:

0.0837

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.0723

Hom.:

155

Bravo

AF:

0.163

Asia WGS

AF:

0.241

AC:

839

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.80

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.71

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.71

Position offset: 1

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