2-112549499-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_019014.6(POLR1B):c.625+117del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 571,242 control chromosomes in the GnomAD database, including 4,063 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (3721 hom., cov: 4)
  • Exomes 𝑓: 0.32 (342 hom.)
• Consequence: POLR1B NM_019014.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

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 -10 ACMG points.

• BP6: Variant 2-112549499-CT-C is Benign according to our data. Variant chr2-112549499-CT-C is described in ClinVar as [Benign]. Clinvar id is 1272934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1B	NM_019014.6	c.625+117del		intron_variant		ENST00000263331.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1B	ENST00000263331.10	c.625+117del		intron_variant		2	NM_019014.6	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 31733 AN: 113572 Hom.: 3721 Cov.: 4

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.319 AC: 146116 AN: 457694 Hom.: 342 AF XY: 0.319 AC XY: 74160 AN XY: 232196

Gnomad4 AFR exome AF: 0.377

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.280 AC: 31741 AN: 113548 Hom.: 3721 Cov.: 4 AF XY: 0.275 AC XY: 14813 AN XY: 53900

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.269

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 17, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34591927; hg19: chr2-113307076;