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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002926.2. 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
	POLR1F	NM_001002926.2	MANE Select	c.958G>A	p.Glu320Lys	missense	Exon 4 of 4	NP_001002926.1	Q3B726

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLR1F	ENST00000222567.6	TSL:1 MANE Select	c.958G>A	p.Glu320Lys	missense	Exon 4 of 4	ENSP00000222567.5	Q3B726
POLR1F	ENST00000944637.1		c.955G>A	p.Glu319Lys	missense	Exon 4 of 4	ENSP00000614696.1
POLR1F	ENST00000462263.1	TSL:2	n.*190G>A		downstream_gene	N/A

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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