chr4-57017009-G-C

Position:

• chr4-57017009-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000938.3(POLR2B):​c.1956-34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 1,379,928 control chromosomes in the GnomAD database, including 542,127 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 0.89 (60317 hom., cov: 31)
  • Exomes 𝑓: 0.88 (481810 hom.)
• Consequence: POLR2B NM_000938.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR2B	NM_000938.3	c.1956-34G>C		intron_variant		ENST00000314595.6	NP_000929.1
POLR2B	NM_001303269.2	c.1935-34G>C		intron_variant			NP_001290198.1
POLR2B	NM_001303268.2	c.1731-34G>C		intron_variant			NP_001290197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR2B	ENST00000314595.6	c.1956-34G>C		intron_variant		1	NM_000938.3	ENSP00000312735.5

Frequencies

GnomAD3 genomes AF: 0.893 AC: 134865 AN: 150948 Hom.: 60273 Cov.: 31

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.844

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.897

GnomAD3 exomes AF: 0.900 AC: 196004 AN: 217856 Hom.: 88403 AF XY: 0.899 AC XY: 107323 AN XY: 119350

Gnomad AFR exome AF: 0.907

Gnomad AMR exome AF: 0.940

Gnomad ASJ exome AF: 0.891

Gnomad EAS exome AF: 0.977

Gnomad SAS exome AF: 0.944

Gnomad FIN exome AF: 0.891

Gnomad NFE exome AF: 0.869

Gnomad OTH exome AF: 0.887

GnomAD4 exome AF: 0.885 AC: 1087482 AN: 1228908 Hom.: 481810 Cov.: 15 AF XY: 0.886 AC XY: 545910 AN XY: 616182

Gnomad4 AFR exome AF: 0.908

Gnomad4 AMR exome AF: 0.935

Gnomad4 ASJ exome AF: 0.894

Gnomad4 EAS exome AF: 0.978

Gnomad4 SAS exome AF: 0.946

Gnomad4 FIN exome AF: 0.890

Gnomad4 NFE exome AF: 0.874

Gnomad4 OTH exome AF: 0.890

GnomAD4 genome AF: 0.894 AC: 134944 AN: 151020 Hom.: 60317 Cov.: 31 AF XY: 0.897 AC XY: 66130 AN XY: 73754

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.919

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.971

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.898

Alfa AF: 0.879 Hom.: 10368

Bravo AF: 0.895

Asia WGS AF: 0.938 AC: 3258 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.60

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: rs1718866; hg19: chr4-57883175;