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_001393919.1(POLR2J):​c.*737G>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_001393919.1 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]

LRWD1 (HGNC:21769): (leucine rich repeats and WD repeat domain containing 1) The protein encoded by this gene interacts with components of the origin recognition complex (ORC) and regulates the formation of the prereplicative complex. The encoded protein stabilizes the ORC and therefore aids in DNA replication. This protein is required for the G1/S phase transition of the cell cycle. In addition, the encoded protein binds to trimethylated histone H3 in heterochromatin and recruits the ORC and lysine methyltransferases, which help maintain the repressive heterochromatic state. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393919.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR2J	NM_006234.6	MANE Select	c.*187G>A		3_prime_UTR	Exon 4 of 4	NP_006225.1
	POLR2J	NM_001393919.1		c.*737G>A		3_prime_UTR	Exon 3 of 3	NP_001380848.1
	POLR2J	NM_001371100.1		c.*187G>A		3_prime_UTR	Exon 3 of 3	NP_001358029.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR2J	ENST00000292614.10	TSL:1 MANE Select	c.*187G>A		3_prime_UTR	Exon 4 of 4	ENSP00000292614.5
	LRWD1	ENST00000922655.1		c.*413C>T		3_prime_UTR	Exon 15 of 15	ENSP00000592714.1
	POLR2J	ENST00000894800.1		c.*187G>A		3_prime_UTR	Exon 4 of 4	ENSP00000564859.1

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 v4.9

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;