Variant chr2-112574844-T-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.2526-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,601,208 control chromosomes in the GnomAD database, including 11,404 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2114 hom., cov: 32)

Exomes 𝑓: 0.099 ( 9290 hom. )

Consequence

POLR1B
NM_019014.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006692

Clinical Significance

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

Conservation

PhyloP100: -0.0740

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=-0.75).

BP6

Variant 2-112574844-T-C is Benign according to our data. Variant chr2-112574844-T-C is described in ClinVar as [Benign]. Clinvar id is 1177727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 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.2526-3T>C		splice_region_variant, 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.2526-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_019014.6	ENSP00000263331	P1	Q9H9Y6-1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21743

AN:

151970

Hom.:

2105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.0700

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.0523

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0754

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.132

AC:

32623

AN:

246606

Hom.:

3102

AF XY:

0.125

AC XY:

16639

AN XY:

133314

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.0717

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.0498

Gnomad NFE exome

AF:

0.0753

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0993

AC:

143915

AN:

1449120

Hom.:

9290

Cov.:

AF XY:

0.0990

AC XY:

71142

AN XY:

718832

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.0724

Gnomad4 EAS exome

AF:

0.314

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.0512

Gnomad4 NFE exome

AF:

0.0816

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.143

AC:

21784

AN:

152088

Hom.:

2114

Cov.:

AF XY:

0.143

AC XY:

10657

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.0700

Gnomad4 EAS

AF:

0.308

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.0523

Gnomad4 NFE

AF:

0.0754

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.0985

Hom.:

662

Bravo

AF:

0.161

Asia WGS

AF:

0.234

AC:

815

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 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000067

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 6

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