NM_006234.6:c.*187G>C

Variant names:

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

Variant summary

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

The NM_006234.6(POLR2J):​c.*187G>C variant causes a 3 prime UTR 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: 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]

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: 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=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006234.6. 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>C		3_prime_UTR	Exon 4 of 4	NP_006225.1
	POLR2J	NM_001393919.1		c.*737G>C		3_prime_UTR	Exon 3 of 3	NP_001380848.1
	POLR2J	NM_001371100.1		c.*187G>C		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>C		3_prime_UTR	Exon 4 of 4	ENSP00000292614.5
	LRWD1	ENST00000922655.1		c.*413C>G		3_prime_UTR	Exon 15 of 15	ENSP00000592714.1
	POLR2J	ENST00000894800.1		c.*187G>C		3_prime_UTR	Exon 4 of 4	ENSP00000564859.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 650280 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 327772

African (AFR) AF: 0.00 AC: 0 AN: 14446

American (AMR) AF: 0.00 AC: 0 AN: 15554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14092

East Asian (EAS) AF: 0.00 AC: 0 AN: 29014

South Asian (SAS) AF: 0.00 AC: 0 AN: 38990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2370

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 476478

Other (OTH) AF: 0.00 AC: 0 AN: 31464

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		0.015

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: rs1131383; hg19: chr7-102113909;