rs1048412

Variant names:

• chr6-30064718-A-G
• rs1048412
• ENST00000471008.5:n.3481A>G

Variant summary

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

The ENST00000471008.5(POLR1H):​n.3481A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,605,336 control chromosomes in the GnomAD database, including 15,601 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 0.17 (2725 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12876 hom.)
• Consequence: POLR1H ENST00000471008.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582
• Publications: 19 publications found

Genes affected

POLR1H (HGNC:13182): (RNA polymerase I subunit H) This gene encodes a DNA-directed RNA polymerase I subunit. The encoded protein contains two potential zinc-binding motifs and may play a role in regulation of cell proliferation. The encoded protein may be involved in cancer and human immunodeficiency virus progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

POLR1HASP (HGNC:):

PPP1R11 (HGNC:9285): (protein phosphatase 1 regulatory inhibitor subunit 11) This gene encodes a specific inhibitor of protein phosphatase-1 (PP1) with a differential sensitivity toward the metal-independent and metal-dependent forms of PP1. The gene is located within the major histocompatibility complex class I region on chromosome 6. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1H	NM_170783.4	c.*21A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000332435.10	NP_740753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1H	ENST00000332435.10	c.*21A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_170783.4	ENSP00000331111.5

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25851 AN: 151996 Hom.: 2710 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0479

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.192

GnomAD2 exomes AF: 0.149 AC: 35981 AN: 241038 AF XY: 0.146

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.0478

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.146

GnomAD4 exome AF: 0.120 AC: 174036 AN: 1453224 Hom.: 12876 Cov.: 29 AF XY: 0.121 AC XY: 87633 AN XY: 723144

African (AFR) AF: 0.273 AC: 9027 AN: 33006

American (AMR) AF: 0.220 AC: 9648 AN: 43844

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 7600 AN: 25964

East Asian (EAS) AF: 0.248 AC: 9698 AN: 39136

South Asian (SAS) AF: 0.165 AC: 14086 AN: 85168

European-Finnish (FIN) AF: 0.0499 AC: 2602 AN: 52146

Middle Eastern (MID) AF: 0.165 AC: 945 AN: 5710

European-Non Finnish (NFE) AF: 0.101 AC: 111782 AN: 1108170

Other (OTH) AF: 0.144 AC: 8648 AN: 60080

GnomAD4 genome AF: 0.170 AC: 25895 AN: 152112 Hom.: 2725 Cov.: 32 AF XY: 0.168 AC XY: 12514 AN XY: 74356

African (AFR) AF: 0.274 AC: 11372 AN: 41458

American (AMR) AF: 0.209 AC: 3197 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3466

East Asian (EAS) AF: 0.186 AC: 962 AN: 5178

South Asian (SAS) AF: 0.182 AC: 881 AN: 4828

European-Finnish (FIN) AF: 0.0479 AC: 507 AN: 10588

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7443 AN: 68004

Other (OTH) AF: 0.189 AC: 398 AN: 2110

Alfa AF: 0.149 Hom.: 3944

Bravo AF: 0.190

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.93
DANN	Benign	0.76
PhyloP100		-0.58
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1048412; hg19: chr6-30032495; COSMIC: COSV60138184; COSMIC: COSV60138184;