Genetic Variant POLR2L:c.*53G>A (chr11-840319-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.587

Publications

48 publications found

Variant links:

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]

POLR2L links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021128.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR2L	NM_021128.5	MANE Select	c.*53G>A		3_prime_UTR	Exon 2 of 2	NP_066951.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POLR2L	ENST00000322028.5	TSL:1 MANE Select	c.*53G>A	3_prime_UTR	Exon 2 of 2	ENSP00000324124.4
POLR2L	ENST00000894693.1		c.*53G>A	3_prime_UTR	Exon 2 of 2	ENSP00000564752.1
POLR2L	ENST00000934860.1		c.*53G>A	3_prime_UTR	Exon 2 of 2	ENSP00000604919.1

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

98989

AN:

151940

Hom.:

33019

Cov.:

show subpopulations

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.:

AF XY:

0.670

AC XY:

350553

AN XY:

523042

show subpopulations

African (AFR)

AF:

0.515

AC:

12815

AN:

24866

American (AMR)

AF:

0.807

AC:

30388

AN:

37648

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

9831

AN:

20268

East Asian (EAS)

AF:

0.889

AC:

31936

AN:

35928

South Asian (SAS)

AF:

0.481

AC:

33757

AN:

70246

European-Finnish (FIN)

AF:

0.751

AC:

36852

AN:

49082

Middle Eastern (MID)

AF:

0.509

AC:

2443

AN:

4798

European-Non Finnish (NFE)

AF:

0.689

AC:

514627

AN:

746402

Other (OTH)

AF:

0.650

AC:

29790

AN:

45826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

10181

20362

30543

40724

50905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11492

22984

34476

45968

57460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.651

AC:

99029

AN:

152058

Hom.:

33031

Cov.:

AF XY:

0.651

AC XY:

48404

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.537

AC:

22252

AN:

41460

American (AMR)

AF:

0.726

AC:

11098

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

1682

AN:

3470

East Asian (EAS)

AF:

0.873

AC:

4522

AN:

5182

South Asian (SAS)

AF:

0.482

AC:

2325

AN:

4826

European-Finnish (FIN)

AF:

0.750

AC:

7922

AN:

10562

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.693

AC:

47093

AN:

67964

Other (OTH)

AF:

0.624

AC:

1315

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1742

3484

5226

6968

8710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.672

Hom.:

56429

Bravo

AF:

0.650

Asia WGS

AF:

0.682

AC:

2370

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.2

(source)

DANN

Benign

0.70

PhyloP100

-0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over