2-112549446-CT-C

Position:

• chr2-112549446-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+60del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.20 (0 hom.)
  • Failed GnomAD Quality Control
• 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-CT-C is Benign according to our data. Variant chr2-112549446-CT-C is described in ClinVar as [Benign]. Clinvar id is 1243148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 353 AN: 131356 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00165

Gnomad ASJ AF: 0.00193

Gnomad EAS AF: 0.000219

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00267

Gnomad OTH AF: 0.00166

GnomAD3 exomes AF: 0.288 AC: 13186 AN: 45842 Hom.: 0 AF XY: 0.298 AC XY: 7743 AN XY: 25966

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.310

Gnomad EAS exome AF: 0.245

Gnomad SAS exome AF: 0.317

Gnomad FIN exome AF: 0.246

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.311

GnomAD4 exome AF: 0.203 AC: 160095 AN: 789578 Hom.: 0 Cov.: 0 AF XY: 0.205 AC XY: 79581 AN XY: 387922

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00270 AC: 355 AN: 131366 Hom.: 0 Cov.: 31 AF XY: 0.00311 AC XY: 197 AN XY: 63288

Gnomad4 AFR AF: 0.00201

Gnomad4 AMR AF: 0.00165

Gnomad4 ASJ AF: 0.00193

Gnomad4 EAS AF: 0.000220

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.00267

Gnomad4 OTH AF: 0.00165

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 14, 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;