dbSNP rs61734275: POLR1F:p.Glu320Lys (chr7-19698375-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001002926.2(POLR1F):c.958G>A(p.Glu320Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,587,614 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

POLR1F
NM_001002926.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.96

Publications

8 publications found

Variant links:

Genes affected

POLR1F (HGNC:18027): (RNA polymerase I subunit F) Predicted to enable DNA-directed 5'-3' RNA polymerase activity. Predicted to be involved in DNA-templated transcription, initiation. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in nucleoplasm. Predicted to be part of RNA polymerase I complex. [provided by Alliance of Genome Resources, Apr 2022]

POLR1F links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033777356).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1F	NM_001002926.2 link	c.958G>A	p.Glu320Lys	missense_variant	Exon 4 of 4	ENST00000222567.6	NP_001002926.1	Q3B726

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1F	ENST00000222567.6 link	c.958G>A	p.Glu320Lys	missense_variant	Exon 4 of 4	1	NM_001002926.2	ENSP00000222567.5		Q3B726
POLR1F	ENST00000462263.1 link	n.*190G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

272

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00635

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000568

AC:

128

AN:

225470

AF XY:

0.000482

show subpopulations

Gnomad AFR exome

AF:

0.00684

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000606

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.000375

GnomAD4 exome

AF:

0.000193

AC:

277

AN:

1435514

Hom.:

Cov.:

AF XY:

0.000156

AC XY:

111

AN XY:

713750

show subpopulations

African (AFR)

AF:

0.00583

AC:

183

AN:

31400

American (AMR)

AF:

0.000467

AC:

AN:

36436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24692

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.0000998

AC:

AN:

80186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5588

European-Non Finnish (NFE)

AF:

0.0000425

AC:

AN:

1105510

Other (OTH)

AF:

0.000372

AC:

AN:

59210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00179

AC:

272

AN:

152100

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

120

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00633

AC:

263

AN:

41518

American (AMR)

AF:

0.000393

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67970

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000918

Hom.:

Bravo

AF:

0.00207

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000642

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.064

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.76

M_CAP

Benign

0.016

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

3.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

REVEL

Benign

0.089

Sift

Uncertain

0.025

Sift4G

Benign

0.12

Polyphen

0.98

Vest4

0.091

MVP

0.48

MPC

0.51

ClinPred

0.051

GERP RS

5.5

Varity_R

0.062

gMVP

0.073

Mutation Taster

=93/7

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over