Variant chr2-112547575-C-T 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+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0084 in 1,613,218 control chromosomes in the GnomAD database, including 277 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 251 hom. )

Consequence

POLR1B
NM_019014.6 splice_region, intron

Scores

Splicing: ADA: 0.0003157

Clinical Significance

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

Conservation

PhyloP100: -0.329

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=-0.79).

BP6

Variant 2-112547575-C-T is Benign according to our data. Variant chr2-112547575-C-T is described in ClinVar as [Benign]. Clinvar id is 1261231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0768 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+8C>T		splice_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+8C>T		splice_region_variant, intron_variant		2	NM_019014.6	ENSP00000263331	P1	Q9H9Y6-1

Frequencies

GnomAD3 genomes

AF:

0.00861

AC:

1310

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00779

Gnomad EAS

AF:

0.0831

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00616

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.0125

AC:

3129

AN:

250514

Hom.:

AF XY:

0.0122

AC XY:

1646

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00253

Gnomad ASJ exome

AF:

0.00678

Gnomad EAS exome

AF:

0.0802

Gnomad SAS exome

AF:

0.00546

Gnomad FIN exome

AF:

0.0260

Gnomad NFE exome

AF:

0.00602

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

AF:

0.00838

AC:

12240

AN:

1460998

Hom.:

251

Cov.:

AF XY:

0.00826

AC XY:

6000

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00258

Gnomad4 ASJ exome

AF:

0.00771

Gnomad4 EAS exome

AF:

0.0987

Gnomad4 SAS exome

AF:

0.00459

Gnomad4 FIN exome

AF:

0.0261

Gnomad4 NFE exome

AF:

0.00503

Gnomad4 OTH exome

AF:

0.00976

GnomAD4 genome

AF:

0.00861

AC:

1311

AN:

152220

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

745

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00779

Gnomad4 EAS

AF:

0.0833

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.0258

Gnomad4 NFE

AF:

0.00616

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00527

Hom.:

Bravo

AF:

0.00717

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 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.7

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00032

dbscSNV1_RF

Benign

0.040

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