rs1718878

Positions:

• chr4-57010789-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000938.3(POLR2B):​c.1590G>A​(p.Ala530Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,604,952 control chromosomes in the GnomAD database, including 100,575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (10569 hom., cov: 33)
  • Exomes 𝑓: 0.35 (90006 hom.)
• Consequence: POLR2B NM_000938.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

Genes affected

POLR2B (HGNC:9188): (RNA polymerase II subunit B) This gene encodes the second largest subunit of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase that catalyzes the transcription of DNA into precursors of mRNA, snRNA and microRNA. This subunit and the largest subunit form opposite sides of the center cleft of Pol II. Deletion of the flap loop region of this subunit results in a decrease in the rate of transcriptional elongation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

POLR2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=2.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR2B	NM_000938.3	c.1590G>A	p.Ala530Ala	synonymous_variant	12/25	ENST00000314595.6	NP_000929.1
POLR2B	NM_001303269.2	c.1569G>A	p.Ala523Ala	synonymous_variant	13/26		NP_001290198.1
POLR2B	NM_001303268.2	c.1365G>A	p.Ala455Ala	synonymous_variant	11/24		NP_001290197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR2B	ENST00000314595.6	c.1590G>A	p.Ala530Ala	synonymous_variant	12/25	1	NM_000938.3	ENSP00000312735.5

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55910 AN: 151882 Hom.: 10561 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.377

GnomAD3 exomes AF: 0.353 AC: 88181 AN: 250148 Hom.: 16105 AF XY: 0.357 AC XY: 48250 AN XY: 135154

Gnomad AFR exome AF: 0.440

Gnomad AMR exome AF: 0.300

Gnomad ASJ exome AF: 0.384

Gnomad EAS exome AF: 0.265

Gnomad SAS exome AF: 0.455

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.349 AC: 506866 AN: 1452952 Hom.: 90006 Cov.: 30 AF XY: 0.352 AC XY: 254198 AN XY: 722908

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.368 AC: 55947 AN: 152000 Hom.: 10569 Cov.: 33 AF XY: 0.368 AC XY: 27342 AN XY: 74278

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.375

Alfa AF: 0.346 Hom.: 12144

Bravo AF: 0.365

Asia WGS AF: 0.385 AC: 1339 AN: 3476

EpiCase AF: 0.354

EpiControl AF: 0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.2
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1718878; hg19: chr4-57876955; COSMIC: COSV58899131;