chr6-30062912-C-A

Variant names:

• chr6-30062912-C-A
• rs1150740
• NM_170783.4:c.356+579C>A

Variant summary

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

The NM_014596.6(POLR1H):​c.356+579C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 149,490 control chromosomes in the GnomAD database, including 592 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 0.084 (592 hom., cov: 28)
• Consequence: POLR1H NM_014596.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• Publications: 17 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014596.6. 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.356+579C>A		intron	N/A	NP_740753.1
	POLR1H	NM_001278785.2		c.356+579C>A		intron	N/A	NP_001265714.1
	POLR1H	NM_001278786.2		c.356+579C>A		intron	N/A	NP_001265715.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1H	ENST00000332435.10	TSL:1 MANE Select	c.356+579C>A		intron	N/A	ENSP00000331111.5
	POLR1H	ENST00000359374.8	TSL:1	c.356+579C>A		intron	N/A	ENSP00000352333.4
	POLR1H	ENST00000471008.5	TSL:1	n.3435+579C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12528 AN: 149400 Hom.: 592 Cov.: 28

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.0442

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.0609

Gnomad NFE AF: 0.0891

Gnomad OTH AF: 0.0894

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0839 AC: 12542 AN: 149490 Hom.: 592 Cov.: 28 AF XY: 0.0838 AC XY: 6113 AN XY: 72964

African (AFR) AF: 0.0624 AC: 2527 AN: 40466

American (AMR) AF: 0.144 AC: 2167 AN: 15014

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 230 AN: 3456

East Asian (EAS) AF: 0.0391 AC: 201 AN: 5140

South Asian (SAS) AF: 0.107 AC: 505 AN: 4710

European-Finnish (FIN) AF: 0.0665 AC: 667 AN: 10036

Middle Eastern (MID) AF: 0.0621 AC: 18 AN: 290

European-Non Finnish (NFE) AF: 0.0891 AC: 6004 AN: 67406

Other (OTH) AF: 0.0886 AC: 183 AN: 2066

Alfa AF: 0.0849 Hom.: 1321

Bravo AF: 0.0905

Asia WGS AF: 0.0700 AC: 244 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		-0.74
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: rs1150740; hg19: chr6-30030689;