2-112549504-T-C

Position:

• chr2-112549504-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019014.6(POLR1B):​c.625+105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 858,036 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (147 hom., cov: 30)
  • Exomes 𝑓: 0.0033 (32 hom.)
• Consequence: POLR1B NM_019014.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-112549504-T-C is Benign according to our data. Variant chr2-112549504-T-C is described in ClinVar as [Benign]. Clinvar id is 1231253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1B	NM_019014.6	c.625+105T>C		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+105T>C		intron_variant		2	NM_019014.6	ENSP00000263331	P1

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3739 AN: 149256 Hom.: 146 Cov.: 30

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.00436

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000836

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.000890

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.00329 AC: 2334 AN: 708672 Hom.: 32 AF XY: 0.00311 AC XY: 1097 AN XY: 352702

Gnomad4 AFR exome AF: 0.0913

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.00382

Gnomad4 EAS exome AF: 0.0000796

Gnomad4 SAS exome AF: 0.000481

Gnomad4 FIN exome AF: 0.0000381

Gnomad4 NFE exome AF: 0.000835

Gnomad4 OTH exome AF: 0.00934

GnomAD4 genome AF: 0.0251 AC: 3743 AN: 149364 Hom.: 147 Cov.: 30 AF XY: 0.0249 AC XY: 1815 AN XY: 73014

Gnomad4 AFR AF: 0.0827

Gnomad4 AMR AF: 0.0194

Gnomad4 ASJ AF: 0.00436

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000837

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000890

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0193 Hom.: 19

Bravo AF: 0.0288

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.6
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs550652481; hg19: chr2-113307081;