6-30061874-C-G

Position:

• chr6-30061874-C-G

Variant summary

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

The NM_170783.4(POLR1H):​c.146-43C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,600,542 control chromosomes in the GnomAD database, including 64,597 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 0.23 (4568 hom., cov: 32)
  • Exomes 𝑓: 0.28 (60029 hom.)
• Consequence: POLR1H NM_170783.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

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]

POLR1H (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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1H	NM_170783.4	c.146-43C>G		intron_variant		ENST00000332435.10	NP_740753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR1H	ENST00000332435.10	c.146-43C>G		intron_variant		1	NM_170783.4	ENSP00000331111.5

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35459 AN: 152000 Hom.: 4556 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.216

GnomAD3 exomes AF: 0.259 AC: 63532 AN: 245040 Hom.: 8580 AF XY: 0.264 AC XY: 35266 AN XY: 133512

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.219

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.270

Gnomad SAS exome AF: 0.287

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.284 AC: 411218 AN: 1448424 Hom.: 60029 Cov.: 28 AF XY: 0.284 AC XY: 204977 AN XY: 721174

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.233 AC: 35483 AN: 152118 Hom.: 4568 Cov.: 32 AF XY: 0.237 AC XY: 17601 AN XY: 74364

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.222

Alfa AF: 0.190 Hom.: 624

Bravo AF: 0.219

Asia WGS AF: 0.313 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.9
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1150741; hg19: chr6-30029651; COSMIC: COSV60138614; COSMIC: COSV60138614;