rs6761

chr17-7514346-C-T

Variant summary

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

The NM_000937.5(POLR2A):c.*167C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 388,410 control chromosomes in the GnomAD database, including 63,600 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 0.55 (23751 hom., cov: 32)
  • Exomes 𝑓: 0.57 (39849 hom.)
• Consequence: POLR2A NM_000937.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR2A	NM_000937.5	c.*167C>T		3_prime_UTR_variant	30/30	ENST00000643490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR2A	ENST00000617998.6	n.6481C>T		non_coding_transcript_exon_variant	29/29	1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83953 AN: 151960 Hom.: 23760 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.575 AC: 135882 AN: 236332 Hom.: 39849 Cov.: 4 AF XY: 0.566 AC XY: 71206 AN XY: 125804

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.606

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.549

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.524

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.570

GnomAD4 genome AF: 0.552 AC: 83958 AN: 152078 Hom.: 23751 Cov.: 32 AF XY: 0.548 AC XY: 40707 AN XY: 74334

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.575

Alfa AF: 0.603 Hom.: 37967

Bravo AF: 0.554

Asia WGS AF: 0.476 AC: 1658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.24
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6761; hg19: chr17-7417663; COSMIC: COSV59494619;