2-112547573-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019014.6(POLR1B):c.492+6G>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,612,890 control chromosomes in the GnomAD database, including 265,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (23239 hom., cov: 31)
  • Exomes 𝑓: 0.57 (242056 hom.)
• Consequence: POLR1B NM_019014.6 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0002779
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.636

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-112547573-G-C is Benign according to our data. Variant chr2-112547573-G-C is described in ClinVar as [Benign]. Clinvar id is 1233209.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1B	NM_019014.6	c.492+6G>C		splice_donor_region_variant, intron_variant		ENST00000263331.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1B	ENST00000263331.10	c.492+6G>C		splice_donor_region_variant, intron_variant		2	NM_019014.6	P1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83420 AN: 151816 Hom.: 23220 Cov.: 31

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.586

GnomAD3 exomes AF: 0.537 AC: 134718 AN: 250680 Hom.: 37182 AF XY: 0.542 AC XY: 73430 AN XY: 135520

Gnomad AFR exome AF: 0.529

Gnomad AMR exome AF: 0.476

Gnomad ASJ exome AF: 0.630

Gnomad EAS exome AF: 0.350

Gnomad SAS exome AF: 0.505

Gnomad FIN exome AF: 0.493

Gnomad NFE exome AF: 0.595

Gnomad OTH exome AF: 0.570

GnomAD4 exome AF: 0.572 AC: 836173 AN: 1460956 Hom.: 242056 Cov.: 49 AF XY: 0.572 AC XY: 415486 AN XY: 726796

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.627

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.563

GnomAD4 genome AF: 0.549 AC: 83479 AN: 151934 Hom.: 23239 Cov.: 31 AF XY: 0.542 AC XY: 40247 AN XY: 74280

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.588

Alfa AF: 0.579 Hom.: 8142

Bravo AF: 0.551

Asia WGS AF: 0.465 AC: 1616 AN: 3478

EpiCase AF: 0.596

EpiControl AF: 0.609

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.14
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.038
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

Other links and lift over

dbSNP: rs11123139; hg19: chr2-113305150; COSMIC: COSV54501898; COSMIC: COSV54501898;