2-112549446-C-CT

Position:

• chr2-112549446-C-CT

Variant summary

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

The NM_019014.6(POLR1B):​c.625+60dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 989,992 control chromosomes in the GnomAD database, including 32 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (26 hom., cov: 31)
  • Exomes 𝑓: 0.076 (6 hom.)
• Consequence: POLR1B NM_019014.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.445

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 2-112549446-C-CT is Benign according to our data. Variant chr2-112549446-C-CT is described in ClinVar as [Benign]. Clinvar id is 1237706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1B	NM_019014.6	c.625+60dup		intron_variant		ENST00000263331.10	NP_061887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1B	ENST00000263331.10	c.625+60dup		intron_variant		2	NM_019014.6	ENSP00000263331	P1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1371 AN: 131632 Hom.: 26 Cov.: 31

Gnomad AFR AF: 0.00295

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00420

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0924

Gnomad SAS AF: 0.00874

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.00370

Gnomad NFE AF: 0.00822

Gnomad OTH AF: 0.00609

GnomAD3 exomes AF: 0.0822 AC: 3767 AN: 45842 Hom.: 0 AF XY: 0.0825 AC XY: 2142 AN XY: 25966

Gnomad AFR exome AF: 0.0634

Gnomad AMR exome AF: 0.0801

Gnomad ASJ exome AF: 0.0851

Gnomad EAS exome AF: 0.130

Gnomad SAS exome AF: 0.0819

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.0683

Gnomad OTH exome AF: 0.0777

GnomAD4 exome AF: 0.0763 AC: 65526 AN: 858350 Hom.: 6 Cov.: 0 AF XY: 0.0763 AC XY: 32238 AN XY: 422380

Gnomad4 AFR exome AF: 0.0713

Gnomad4 AMR exome AF: 0.0661

Gnomad4 ASJ exome AF: 0.0794

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.0723

Gnomad4 FIN exome AF: 0.0910

Gnomad4 NFE exome AF: 0.0733

Gnomad4 OTH exome AF: 0.0791

GnomAD4 genome AF: 0.0104 AC: 1373 AN: 131642 Hom.: 26 Cov.: 31 AF XY: 0.0120 AC XY: 759 AN XY: 63444

Gnomad4 AFR AF: 0.00297

Gnomad4 AMR AF: 0.00420

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.0929

Gnomad4 SAS AF: 0.00880

Gnomad4 FIN AF: 0.0284

Gnomad4 NFE AF: 0.00822

Gnomad4 OTH AF: 0.00606

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

Jun 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs376484413; hg19: chr2-113307023;