19-45406676-G-A

Variant names:

• chr19-45406676-G-A
• rs967591
• NM_012099.3:c.-21G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 54 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012099.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1G	NM_012099.3	MANE Select	c.-21G>A		5_prime_UTR	Exon 1 of 3	NP_036231.1
	POLR1G	NM_001297590.3		c.-21G>A		5_prime_UTR	Exon 1 of 3	NP_001284519.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1G	ENST00000309424.8	TSL:1 MANE Select	c.-21G>A		5_prime_UTR	Exon 1 of 3	ENSP00000310966.3
	POLR1G	ENST00000592852.1	TSL:2	c.-930G>A		5_prime_UTR	Exon 1 of 2	ENSP00000467771.1
	POLR1G	ENST00000589804.1	TSL:1	c.-21G>A		upstream_gene	N/A	ENSP00000465099.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29388 AN: 152010 Hom.: 3049 Cov.: 32

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

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.: 31 AF XY: 0.185 AC XY: 126983 AN XY: 686536

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

GnomAD4 genome AF: 0.193 AC: 29395 AN: 152128 Hom.: 3051 Cov.: 32 AF XY: 0.198 AC XY: 14731 AN XY: 74354

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: 58 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11156 AN: 68008

Other (OTH) AF: 0.191 AC: 404 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.1
DANN	Benign	0.60
PhyloP100		0.035
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs967591; hg19: chr19-45909934; COSMIC: COSV56232928; COSMIC: COSV56232928;