rs3787016

Variant names:

• chr19-1090804-A-C
• rs3787016
• NM_002695.5:c.429+104T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-1090804-A-C
• chr19-1090804-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002695.5(POLR2E):​c.429+104T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POLR2E NM_002695.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24
• Publications: 62 publications found

Genes affected

POLR2E (HGNC:9192): (RNA polymerase II, I and III subunit E) This gene encodes the fifth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA-directed RNA polymerases and is present in two-fold molar excess over the other polymerase subunits. An interaction between this subunit and a hepatitis virus transactivating protein has been demonstrated, suggesting that interaction between transcriptional activators and the polymerase can occur through this subunit. A pseudogene is located on chromosome 11. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR2E	NM_002695.5	c.429+104T>G		intron_variant	Intron 4 of 7	ENST00000615234.5	NP_002686.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR2E	ENST00000615234.5	c.429+104T>G		intron_variant	Intron 4 of 7	1	NM_002695.5	ENSP00000478303.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 821862 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 420668

African (AFR) AF: 0.00 AC: 0 AN: 20346

American (AMR) AF: 0.00 AC: 0 AN: 30402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18372

East Asian (EAS) AF: 0.00 AC: 0 AN: 33552

South Asian (SAS) AF: 0.00 AC: 0 AN: 61798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4458

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 580948

Other (OTH) AF: 0.00 AC: 0 AN: 38774

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.21
DANN	Benign	0.21
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs3787016; hg19: chr19-1090803;