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2-112550939-T-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_019014.6(POLR1B):c.699T>A(p.Thr233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 1,612,808 control chromosomes in the GnomAD database, including 392,015 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.64 ( 31984 hom., cov: 32)
Exomes 𝑓: 0.70 ( 360031 hom. )

Consequence

POLR1B
NM_019014.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.92
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-112550939-T-A is Benign according to our data. Variant chr2-112550939-T-A is described in ClinVar as [Benign]. Clinvar id is 1178754.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.92 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
POLR1BNM_019014.6 linkuse as main transcriptc.699T>A p.Thr233= synonymous_variant 5/15 ENST00000263331.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
POLR1BENST00000263331.10 linkuse as main transcriptc.699T>A p.Thr233= synonymous_variant 5/152 NM_019014.6 P1Q9H9Y6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.641
AC:
97347
AN:
151940
Hom.:
31974
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.552
Gnomad AMI
AF:
0.654
Gnomad AMR
AF:
0.585
Gnomad ASJ
AF:
0.766
Gnomad EAS
AF:
0.363
Gnomad SAS
AF:
0.670
Gnomad FIN
AF:
0.601
Gnomad MID
AF:
0.769
Gnomad NFE
AF:
0.724
Gnomad OTH
AF:
0.676
GnomAD3 exomes
AF:
0.644
AC:
161896
AN:
251426
Hom.:
53934
AF XY:
0.655
AC XY:
89043
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.551
Gnomad AMR exome
AF:
0.528
Gnomad ASJ exome
AF:
0.763
Gnomad EAS exome
AF:
0.351
Gnomad SAS exome
AF:
0.675
Gnomad FIN exome
AF:
0.604
Gnomad NFE exome
AF:
0.727
Gnomad OTH exome
AF:
0.676
GnomAD4 exome
AF:
0.697
AC:
1018421
AN:
1460750
Hom.:
360031
Cov.:
45
AF XY:
0.698
AC XY:
507593
AN XY:
726750
show subpopulations
Gnomad4 AFR exome
AF:
0.556
Gnomad4 AMR exome
AF:
0.536
Gnomad4 ASJ exome
AF:
0.758
Gnomad4 EAS exome
AF:
0.341
Gnomad4 SAS exome
AF:
0.680
Gnomad4 FIN exome
AF:
0.605
Gnomad4 NFE exome
AF:
0.726
Gnomad4 OTH exome
AF:
0.678
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.641
AC:
97395
AN:
152058
Hom.:
31984
Cov.:
32
AF XY:
0.634
AC XY:
47115
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.552
Gnomad4 AMR
AF:
0.585
Gnomad4 ASJ
AF:
0.766
Gnomad4 EAS
AF:
0.361
Gnomad4 SAS
AF:
0.669
Gnomad4 FIN
AF:
0.601
Gnomad4 NFE
AF:
0.724
Gnomad4 OTH
AF:
0.677
Alfa
AF:
0.706
Hom.:
12300
Bravo
AF:
0.633
Asia WGS
AF:
0.522
AC:
1814
AN:
3478
EpiCase
AF:
0.724
EpiControl
AF:
0.733

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 submitterclinical testingGeneDxMay 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
Cadd
Benign
0.18
Dann
Benign
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs2304555; hg19: chr2-113308516; COSMIC: COSV54498737; COSMIC: COSV54498737; API