7-102473462-C-T

Variant names:

• chr7-102473462-C-T
• rs1131383
• NM_006234.6:c.*187G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006234.6(POLR2J):​c.*187G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 795,656 control chromosomes in the GnomAD database, including 244,096 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 0.75 (39903 hom., cov: 32)
  • Exomes 𝑓: 0.80 (204193 hom.)
• Consequence: POLR2J NM_006234.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 31 publications found

Genes affected

POLR2J (HGNC:9197): (RNA polymerase II subunit J) This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene exists as a heterodimer with another polymerase subunit; together they form a core subassembly unit of the polymerase. Two similar genes are located nearby on chromosome 7q22.1 and a pseudogene is found on chromosome 7p13. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR2J	NM_006234.6	c.*187G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000292614.10	NP_006225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR2J	ENST00000292614.10	c.*187G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_006234.6	ENSP00000292614.5

Frequencies

GnomAD3 genomes AF: 0.747 AC: 109246 AN: 146306 Hom.: 39896 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.735

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.802 AC: 520377 AN: 649234 Hom.: 204193 Cov.: 9 AF XY: 0.798 AC XY: 261287 AN XY: 327288

African (AFR) AF: 0.627 AC: 9031 AN: 14402

American (AMR) AF: 0.842 AC: 13061 AN: 15518

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 11396 AN: 14074

East Asian (EAS) AF: 0.868 AC: 25119 AN: 28950

South Asian (SAS) AF: 0.707 AC: 27473 AN: 38862

European-Finnish (FIN) AF: 0.799 AC: 22243 AN: 27834

Middle Eastern (MID) AF: 0.751 AC: 1775 AN: 2364

European-Non Finnish (NFE) AF: 0.810 AC: 385336 AN: 475822

Other (OTH) AF: 0.794 AC: 24943 AN: 31408

GnomAD4 genome AF: 0.747 AC: 109306 AN: 146422 Hom.: 39903 Cov.: 32 AF XY: 0.749 AC XY: 53633 AN XY: 71592

African (AFR) AF: 0.620 AC: 24097 AN: 38874

American (AMR) AF: 0.825 AC: 12353 AN: 14966

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2692 AN: 3364

East Asian (EAS) AF: 0.851 AC: 4304 AN: 5058

South Asian (SAS) AF: 0.687 AC: 3073 AN: 4474

European-Finnish (FIN) AF: 0.800 AC: 8266 AN: 10336

Middle Eastern (MID) AF: 0.729 AC: 207 AN: 284

European-Non Finnish (NFE) AF: 0.788 AC: 52115 AN: 66152

Other (OTH) AF: 0.751 AC: 1533 AN: 2042

Alfa AF: 0.755 Hom.: 129915

Bravo AF: 0.720

Asia WGS AF: 0.698 AC: 2426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.74
PhyloP100		0.015
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1131383; hg19: chr7-102113909;