rs8321

Variant names:

• chr6-30064745-A-C
• rs8321
• ENST00000471008.5:n.3508A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-30064745-A-C
• chr6-30064745-A-T

Variant summary

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

The ENST00000471008.5(POLR1H):​n.3508A>C 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 0.095 in 1,578,700 control chromosomes in the GnomAD database, including 9,280 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 0.057 (426 hom., cov: 32)
  • Exomes 𝑓: 0.099 (8854 hom.)
• Consequence: POLR1H ENST00000471008.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 66 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1H	NM_170783.4	c.*48A>C		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.*48A>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_170783.4	ENSP00000331111.5

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8746 AN: 152116 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0369

GnomAD2 exomes AF: 0.0541 AC: 12656 AN: 233902 AF XY: 0.0540

Gnomad AFR exome AF: 0.0157

Gnomad AMR exome AF: 0.0167

Gnomad ASJ exome AF: 0.0293

Gnomad EAS exome AF: 0.0000584

Gnomad FIN exome AF: 0.0529

Gnomad NFE exome AF: 0.0956

Gnomad OTH exome AF: 0.0533

GnomAD4 exome AF: 0.0990 AC: 141181 AN: 1426466 Hom.: 8854 Cov.: 24 AF XY: 0.0954 AC XY: 67882 AN XY: 711216

African (AFR) AF: 0.0142 AC: 453 AN: 31970

American (AMR) AF: 0.0176 AC: 744 AN: 42234

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 769 AN: 25604

East Asian (EAS) AF: 0.000129 AC: 5 AN: 38630

South Asian (SAS) AF: 0.000180 AC: 15 AN: 83358

European-Finnish (FIN) AF: 0.0554 AC: 2869 AN: 51744

Middle Eastern (MID) AF: 0.00424 AC: 24 AN: 5666

European-Non Finnish (NFE) AF: 0.121 AC: 131483 AN: 1088116

Other (OTH) AF: 0.0815 AC: 4819 AN: 59144

GnomAD4 genome AF: 0.0574 AC: 8743 AN: 152234 Hom.: 426 Cov.: 32 AF XY: 0.0518 AC XY: 3860 AN XY: 74450

African (AFR) AF: 0.0146 AC: 605 AN: 41554

American (AMR) AF: 0.0234 AC: 358 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.0531 AC: 563 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6911 AN: 67990

Other (OTH) AF: 0.0365 AC: 77 AN: 2108

Alfa AF: 0.0885 Hom.: 3214

Bravo AF: 0.0539

Asia WGS AF: 0.00318 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.79
PhyloP100		0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs8321; hg19: chr6-30032522;