dbSNP rs967591: POLR1G:c.-21G>A (chr19-45406676-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_012099.3(POLR1G):c.-21G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,543,840 control chromosomes in the GnomAD database, including 28,516 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 0.19 ( 3051 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25465 hom. )

Consequence

POLR1G
NM_012099.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0350

Publications

54 publications found

Variant links:

Genes affected

POLR1G (HGNC:24219): (RNA polymerase I subunit G) Enables RNA binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within rRNA transcription. Located in cytosol; mitochondrion; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

POLR1G 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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1G	NM_012099.3 link	c.-21G>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000309424.8	NP_036231.1
POLR1G	NM_001297590.3 link	c.-21G>A		5_prime_UTR_variant	Exon 1 of 3		NP_001284519.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
POLR1G	ENST00000309424.8 link	c.-21G>A	5_prime_UTR_variant	Exon 1 of 3	1	NM_012099.3	ENSP00000310966.3
POLR1G	ENST00000592852.1 link	c.-930G>A	5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000467771.1
POLR1G	ENST00000589804.1 link	c.-21G>A	upstream_gene_variant		1		ENSP00000465099.1
POLR1G	ENST00000590794.1 link	c.-24G>A	upstream_gene_variant		5		ENSP00000466503.1

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29388

AN:

152010

Hom.:

3049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.444

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.193

GnomAD2 exomes

AF:

0.218

AC:

32518

AN:

149122

AF XY:

0.219

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.183

AC:

254126

AN:

1391712

Hom.:

25465

Cov.:

AF XY:

0.185

AC XY:

126983

AN XY:

686536

show subpopulations

African (AFR)

AF:

0.192

AC:

5943

AN:

30934

American (AMR)

AF:

0.255

AC:

8827

AN:

34582

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

4861

AN:

24952

East Asian (EAS)

AF:

0.457

AC:

15740

AN:

34418

South Asian (SAS)

AF:

0.265

AC:

20841

AN:

78602

European-Finnish (FIN)

AF:

0.206

AC:

10119

AN:

49200

Middle Eastern (MID)

AF:

0.170

AC:

920

AN:

5412

European-Non Finnish (NFE)

AF:

0.164

AC:

175922

AN:

1075938

Other (OTH)

AF:

0.190

AC:

10953

AN:

57674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

9769

19539

29308

39078

48847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6566

13132

19698

26264

32830

<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:

0.193

AC:

29395

AN:

152128

Hom.:

3051

Cov.:

AF XY:

0.198

AC XY:

14731

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.192

AC:

7984

AN:

41530

American (AMR)

AF:

0.217

AC:

3311

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

646

AN:

3466

East Asian (EAS)

AF:

0.444

AC:

2290

AN:

5158

South Asian (SAS)

AF:

0.273

AC:

1316

AN:

4816

European-Finnish (FIN)

AF:

0.200

AC:

2114

AN:

10580

Middle Eastern (MID)

AF:

0.199

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.164

AC:

11156

AN:

68008

Other (OTH)

AF:

0.191

AC:

404

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1181

2361

3542

4722

5903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.174

Hom.:

4453

Bravo

AF:

0.192

Asia WGS

AF:

0.333

AC:

1157

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.1

(source)

DANN

Benign

0.60

PhyloP100

0.035

PromoterAI

-0.17

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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