chr6-30064896-A-G

Position:

• chr6-30064896-A-G

Variant summary

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

The NM_170783.4(POLR1H):​c.*199A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 433,336 control chromosomes in the GnomAD database, including 2,756 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 0.12 (1505 hom., cov: 32)
  • Exomes 𝑓: 0.078 (1251 hom.)
• Consequence: POLR1H NM_170783.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR1H	NM_170783.4	c.*199A>G		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.*199A>G		3_prime_UTR_variant	4/4	1	NM_170783.4	ENSP00000331111.5

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17941 AN: 152072 Hom.: 1496 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0579

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.0784 AC: 22047 AN: 281146 Hom.: 1251 Cov.: 4 AF XY: 0.0774 AC XY: 11267 AN XY: 145608

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0266

Gnomad4 NFE exome AF: 0.0565

Gnomad4 OTH exome AF: 0.0971

GnomAD4 genome AF: 0.118 AC: 17973 AN: 152190 Hom.: 1505 Cov.: 32 AF XY: 0.116 AC XY: 8657 AN XY: 74416

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0579

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0750 Hom.: 895

Bravo AF: 0.136

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.3
DANN	Benign	0.86

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: rs3188482; hg19: chr6-30032673;