2-112542753-G-A

Position:

• chr2-112542753-G-A

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.177+82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,522,762 control chromosomes in the GnomAD database, including 353,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37178 hom., cov: 33)
  • Exomes 𝑓: 0.68 (316278 hom.)
• Consequence: POLR1B NM_019014.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.732

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=-0.91).
• BP6: Variant 2-112542753-G-A is Benign according to our data. Variant chr2-112542753-G-A is described in ClinVar as [Benign]. Clinvar id is 1251680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1B	NM_019014.6	c.177+82G>A		intron_variant		ENST00000263331.10	NP_061887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1B	ENST00000263331.10	c.177+82G>A		intron_variant		2	NM_019014.6	ENSP00000263331	P1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105937 AN: 152034 Hom.: 37139 Cov.: 33

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.678 AC: 929854 AN: 1370610 Hom.: 316278 Cov.: 23 AF XY: 0.677 AC XY: 458751 AN XY: 677574

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.705

Gnomad4 ASJ exome AF: 0.715

Gnomad4 EAS exome AF: 0.661

Gnomad4 SAS exome AF: 0.641

Gnomad4 FIN exome AF: 0.572

Gnomad4 NFE exome AF: 0.681

Gnomad4 OTH exome AF: 0.686

GnomAD4 genome AF: 0.697 AC: 106029 AN: 152152 Hom.: 37178 Cov.: 33 AF XY: 0.691 AC XY: 51370 AN XY: 74376

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.728

Alfa AF: 0.571 Hom.: 1752

Bravo AF: 0.713

Asia WGS AF: 0.707 AC: 2457 AN: 3478

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	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4849071; hg19: chr2-113300330;