rs8321

Positions:

• chr6-30064745-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000332435.10(POLR1H):​c.*48A>C variant causes a 3 prime UTR 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 ENST00000332435.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

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]

PPP1R11 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
POLR1H	NM_170783.4	c.*48A>C		3_prime_UTR_variant	4/4	ENST00000332435.10	NP_740753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1H	ENST00000332435.10	c.*48A>C		3_prime_UTR_variant	4/4	1	NM_170783.4	ENSP00000331111	P1

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

GnomAD3 exomes AF: 0.0541 AC: 12656 AN: 233902 Hom.: 601 AF XY: 0.0540 AC XY: 6928 AN XY: 128232

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 SAS exome AF: 0.0000712

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

Gnomad4 AFR exome AF: 0.0142

Gnomad4 AMR exome AF: 0.0176

Gnomad4 ASJ exome AF: 0.0300

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.000180

Gnomad4 FIN exome AF: 0.0554

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.0815

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

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0887 Hom.: 1322

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs8321; hg19: chr6-30032522;