2-112542424-TTCCGGCGTGTACCGAGAGACTGGCG-T

Position:

• chr2-112542424-TTCCGGCGTGTACCGAGAGACTGGCG-T

Variant summary

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

The ENST00000409894.7(POLR1B):​c.-40_-16del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 151,786 control chromosomes in the GnomAD database, including 884 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.090 (884 hom., cov: 31)
  • Exomes 𝑓: 0.094 (8332 hom.)
  • Failed GnomAD Quality Control
• Consequence: POLR1B ENST00000409894.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.20

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 2-112542424-TTCCGGCGTGTACCGAGAGACTGGCG-T is Benign according to our data. Variant chr2-112542424-TTCCGGCGTGTACCGAGAGACTGGCG-T is described in ClinVar as [Benign]. Clinvar id is 2497901.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1B	NM_019014.6			upstream_gene_variant		ENST00000263331.10	NP_061887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1B	ENST00000263331.10			upstream_gene_variant		2	NM_019014.6	ENSP00000263331	P1

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13712 AN: 151668 Hom.: 878 Cov.: 31

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0790

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.0869

GnomAD3 exomes AF: 0.118 AC: 29013 AN: 246852 Hom.: 2378 AF XY: 0.113 AC XY: 15227 AN XY: 134380

Gnomad AFR exome AF: 0.0512

Gnomad AMR exome AF: 0.210

Gnomad ASJ exome AF: 0.0835

Gnomad EAS exome AF: 0.328

Gnomad SAS exome AF: 0.132

Gnomad FIN exome AF: 0.0731

Gnomad NFE exome AF: 0.0720

Gnomad OTH exome AF: 0.101

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0940 AC: 137312 AN: 1460466 Hom.: 8332 AF XY: 0.0943 AC XY: 68479 AN XY: 726534

Gnomad4 AFR exome AF: 0.0545

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.0863

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.0762

Gnomad4 NFE exome AF: 0.0805

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0905 AC: 13732 AN: 151786 Hom.: 884 Cov.: 31 AF XY: 0.0928 AC XY: 6880 AN XY: 74156

Gnomad4 AFR AF: 0.0593

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0790

Gnomad4 NFE AF: 0.0753

Gnomad4 OTH AF: 0.0869

Alfa AF: 0.0771 Hom.: 96

Bravo AF: 0.0976

Asia WGS AF: 0.222 AC: 772 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

Mar 22, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs138896228; hg19: chr2-113300001;