11-840319-C-T

Position:

• chr11-840319-C-T

Variant summary

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

The NM_021128.5(POLR2L):​c.*53G>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 0.675 in 1,187,122 control chromosomes in the GnomAD database, including 275,643 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 0.65 (33031 hom., cov: 33)
  • Exomes 𝑓: 0.68 (242612 hom.)
• Consequence: POLR2L NM_021128.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587

Genes affected

POLR2L (HGNC:9199): (RNA polymerase II, I and III subunit L) This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR2L	NM_021128.5	c.*53G>A		3_prime_UTR_variant	2/2	ENST00000322028.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR2L	ENST00000322028.5	c.*53G>A		3_prime_UTR_variant	2/2	1	NM_021128.5	P1
POLR2L	ENST00000534030.1	c.*53G>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	4

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98989 AN: 151940 Hom.: 33019 Cov.: 33

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.679 AC: 702439 AN: 1035064 Hom.: 242612 Cov.: 13 AF XY: 0.670 AC XY: 350553 AN XY: 523042

Gnomad4 AFR exome AF: 0.515

Gnomad4 AMR exome AF: 0.807

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.889

Gnomad4 SAS exome AF: 0.481

Gnomad4 FIN exome AF: 0.751

Gnomad4 NFE exome AF: 0.689

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.651 AC: 99029 AN: 152058 Hom.: 33031 Cov.: 33 AF XY: 0.651 AC XY: 48404 AN XY: 74304

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.873

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.624

Alfa AF: 0.675 Hom.: 44581

Bravo AF: 0.650

Asia WGS AF: 0.682 AC: 2370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3059; hg19: chr11-840319; COSMIC: COSV58991140; COSMIC: COSV58991140;