Variant rs967591 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
POLR1G	NM_012099.3 link	c.-21G>A		5_prime_UTR_variant	1/3	ENST00000309424.8	NP_036231.1	O15446-1
POLR1G	NM_001297590.3 link	c.-21G>A		5_prime_UTR_variant	1/3		NP_001284519.1	O15446-2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
POLR1G	ENST00000309424 link	c.-21G>A	5_prime_UTR_variant	1/3	1	NM_012099.3	ENSP00000310966.3	O15446-1
POLR1G	ENST00000592852 link	c.-930G>A	5_prime_UTR_variant	1/2	2		ENSP00000467771.1	K7EQC8
POLR1G	ENST00000589804.1 link	c.-21G>A	upstream_gene_variant		1		ENSP00000465099.1	O15446-2
POLR1G	ENST00000590794.1 link	c.-24G>A	upstream_gene_variant		5		ENSP00000466503.1	K7EMH2

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

GnomAD3 exomes

AF:

0.218

AC:

32518

AN:

149122

Hom.:

4016

AF XY:

0.219

AC XY:

17252

AN XY:

78820

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 SAS exome

AF:

0.265

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

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.457

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.206

Gnomad4 NFE exome

AF:

0.164

Gnomad4 OTH exome

AF:

0.190

GnomAD4 genome

AF:

0.193

AC:

29395

AN:

152128

Hom.:

3051

Cov.:

AF XY:

0.198

AC XY:

14731

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.444

Gnomad4 SAS

AF:

0.273

Gnomad4 FIN

AF:

0.200

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.151

Hom.:

798

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

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over