rs8071847

Positions:

• chr17-7504008-A-G

Variant summary

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

The NM_000937.5(POLR2A):​c.3240+217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 353,180 control chromosomes in the GnomAD database, including 7,716 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 0.19 (2973 hom., cov: 31)
  • Exomes 𝑓: 0.21 (4743 hom.)
• Consequence: POLR2A NM_000937.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

Genes affected

POLR2A (HGNC:9187): (RNA polymerase II subunit A) This gene encodes the largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains a carboxy terminal domain composed of heptapeptide repeats that are essential for polymerase activity. These repeats contain serine and threonine residues that are phosphorylated in actively transcribing RNA polymerase. In addition, this subunit, in combination with several other polymerase subunits, forms the DNA binding domain of the polymerase, a groove in which the DNA template is transcribed into RNA. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR2A	NM_000937.5	c.3240+217A>G		intron_variant		ENST00000643490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR2A	ENST00000674977.2	c.3240+217A>G		intron_variant				P1
POLR2A	ENST00000617998.6	n.3639+217A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29128 AN: 151916 Hom.: 2977 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0278

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.207 AC: 41640 AN: 201146 Hom.: 4743 AF XY: 0.214 AC XY: 23625 AN XY: 110448

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.0322

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.192 AC: 29129 AN: 152034 Hom.: 2973 Cov.: 31 AF XY: 0.188 AC XY: 13977 AN XY: 74328

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0278

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.208

Alfa AF: 0.208 Hom.: 6805

Bravo AF: 0.193

Asia WGS AF: 0.136 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.35

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: rs8071847; hg19: chr17-7407327;