chr6-30064896-A-G

Variant names:

• chr6-30064896-A-G
• rs3188482
• NM_170783.4:c.*199A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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]

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]

POLR1HASP (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170783.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1H	NM_170783.4	MANE Select	c.*199A>G		3_prime_UTR	Exon 4 of 4	NP_740753.1	Q9P1U0
	POLR1H	NM_001278785.2		c.*199A>G		3_prime_UTR	Exon 5 of 5	NP_001265714.1	Q9P1U0
	POLR1H	NM_001278786.2		c.*199A>G		3_prime_UTR	Exon 5 of 5	NP_001265715.1	Q9P1U0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1H	ENST00000332435.10	TSL:1 MANE Select	c.*199A>G		3_prime_UTR	Exon 4 of 4	ENSP00000331111.5	Q9P1U0
	POLR1H	ENST00000359374.8	TSL:1	c.*199A>G		3_prime_UTR	Exon 5 of 5	ENSP00000352333.4	Q9P1U0
	POLR1H	ENST00000471008.5	TSL:1	n.3659A>G		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AF: 0.223 AC: 1688 AN: 7584

American (AMR) AF: 0.152 AC: 1213 AN: 7970

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 1231 AN: 9960

East Asian (EAS) AF: 0.165 AC: 3828 AN: 23144

South Asian (SAS) AF: 0.120 AC: 1457 AN: 12160

European-Finnish (FIN) AF: 0.0266 AC: 596 AN: 22404

Middle Eastern (MID) AF: 0.124 AC: 232 AN: 1870

European-Non Finnish (NFE) AF: 0.0565 AC: 10053 AN: 178044

Other (OTH) AF: 0.0971 AC: 1749 AN: 18010

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

African (AFR) AF: 0.225 AC: 9311 AN: 41466

American (AMR) AF: 0.141 AC: 2163 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3470

East Asian (EAS) AF: 0.149 AC: 772 AN: 5190

South Asian (SAS) AF: 0.158 AC: 763 AN: 4816

European-Finnish (FIN) AF: 0.0238 AC: 253 AN: 10618

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0579 AC: 3936 AN: 68018

Other (OTH) AF: 0.130 AC: 275 AN: 2114

Alfa AF: 0.0826 Hom.: 2786

Bravo AF: 0.136

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.3
DANN	Benign	0.86
PhyloP100		-0.44
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: rs3188482; hg19: chr6-30032673;