2-112550841-A-T

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.626-25A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,609,814 control chromosomes in the GnomAD database, including 310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (16 hom., cov: 33)
  • Exomes 𝑓: 0.013 (294 hom.)
• Consequence: POLR1B NM_019014.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610

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 2-112550841-A-T is Benign according to our data. Variant chr2-112550841-A-T is described in ClinVar as [Benign]. Clinvar id is 1260159.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1B	NM_019014.6	c.626-25A>T		intron_variant		ENST00000263331.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1B	ENST00000263331.10	c.626-25A>T		intron_variant		2	NM_019014.6	P1

Frequencies

GnomAD3 genomes AF: 0.00836 AC: 1272 AN: 152168 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00987

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.0127 AC: 3159 AN: 248158 Hom.: 71 AF XY: 0.0153 AC XY: 2054 AN XY: 134196

Gnomad AFR exome AF: 0.00198

Gnomad AMR exome AF: 0.00357

Gnomad ASJ exome AF: 0.00202

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0597

Gnomad FIN exome AF: 0.00482

Gnomad NFE exome AF: 0.00919

Gnomad OTH exome AF: 0.00812

GnomAD4 exome AF: 0.0132 AC: 19223 AN: 1457528 Hom.: 294 Cov.: 29 AF XY: 0.0145 AC XY: 10519 AN XY: 724962

Gnomad4 AFR exome AF: 0.00148

Gnomad4 AMR exome AF: 0.00341

Gnomad4 ASJ exome AF: 0.00169

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0604

Gnomad4 FIN exome AF: 0.00497

Gnomad4 NFE exome AF: 0.0115

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.00835 AC: 1272 AN: 152286 Hom.: 16 Cov.: 33 AF XY: 0.00927 AC XY: 690 AN XY: 74466

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0682

Gnomad4 FIN AF: 0.00415

Gnomad4 NFE AF: 0.00987

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00798 Hom.: 2

Bravo AF: 0.00670

Asia WGS AF: 0.0180 AC: 63 AN: 3478

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 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.6
Dann	Benign	0.79
La Branchor		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs149363725; hg19: chr2-113308418;