Genetic Variant POLR1G:c.-21G>C (chr19-45406676-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012099.3(POLR1G):c.-21G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000388 in 1,545,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000036 ( 0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1G	NM_012099.3 link	c.-21G>C		5_prime_UTR_variant	Exon 1 of 3	ENST00000309424.8	NP_036231.1
POLR1G	NM_001297590.3 link	c.-21G>C		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>C	5_prime_UTR_variant	Exon 1 of 3	1	NM_012099.3	ENSP00000310966.3
POLR1G	ENST00000592852.1 link	c.-930G>C	5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000467771.1
POLR1G	ENST00000589804.1 link	c.-21G>C	upstream_gene_variant		1		ENSP00000465099.1
POLR1G	ENST00000590794.1 link	c.-24G>C	upstream_gene_variant		5		ENSP00000466503.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000359

AC:

AN:

1393140

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

687214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30970

American (AMR)

AF:

0.00

AC:

AN:

34696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24972

East Asian (EAS)

AF:

0.00

AC:

AN:

34504

South Asian (SAS)

AF:

0.00

AC:

AN:

78724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5418

European-Non Finnish (NFE)

AF:

0.00000464

AC:

AN:

1076910

Other (OTH)

AF:

0.00

AC:

AN:

57728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

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:

0.00000658

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

4453

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

(source)

DANN

Benign

0.46

PhyloP100

0.035

PromoterAI

-0.026

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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