2-112549538-C-T

Position:

• chr2-112549538-C-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.625+139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 661,486 control chromosomes in the GnomAD database, including 158,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (31799 hom., cov: 21)
  • Exomes 𝑓: 0.69 (126923 hom.)
• Consequence: POLR1B NM_019014.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.312

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=-1.01).
• BP6: Variant 2-112549538-C-T is Benign according to our data. Variant chr2-112549538-C-T is described in ClinVar as [Benign]. Clinvar id is 1258590.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1B	NM_019014.6	c.625+139C>T		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+139C>T		intron_variant		2	NM_019014.6	ENSP00000263331	P1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 95076 AN: 144964 Hom.: 31795 Cov.: 21

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.795

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.687

GnomAD4 exome AF: 0.688 AC: 355111 AN: 516450 Hom.: 126923 AF XY: 0.688 AC XY: 181131 AN XY: 263348

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.552

Gnomad4 ASJ exome AF: 0.757

Gnomad4 EAS exome AF: 0.315

Gnomad4 SAS exome AF: 0.676

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.725

Gnomad4 OTH exome AF: 0.676

GnomAD4 genome AF: 0.656 AC: 95103 AN: 145036 Hom.: 31799 Cov.: 21 AF XY: 0.650 AC XY: 45645 AN XY: 70230

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.688

Alfa AF: 0.678 Hom.: 4397

Bravo AF: 0.643

Asia WGS AF: 0.532 AC: 1844 AN: 3468

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.54

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: rs11675730; hg19: chr2-113307115;