6-30063568-T-C

Variant names:

• chr6-30063568-T-C
• rs1150739
• NM_170783.4:c.357-1105T>C

Variant summary

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

The NM_170783.4(POLR1H):​c.357-1105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,574 control chromosomes in the GnomAD database, including 13,270 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 0.42 (13270 hom., cov: 31)
• Consequence: POLR1H NM_170783.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 26 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 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.357-1105T>C		intron	N/A	NP_740753.1
	POLR1H	NM_001278785.2		c.357-1105T>C		intron	N/A	NP_001265714.1
	POLR1H	NM_001278786.2		c.357-1105T>C		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.357-1105T>C		intron	N/A	ENSP00000331111.5
	POLR1H	ENST00000359374.8	TSL:1	c.357-1105T>C		intron	N/A	ENSP00000352333.4
	POLR1H	ENST00000471008.5	TSL:1	n.3436-1105T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63257 AN: 151460 Hom.: 13238 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.418 AC: 63332 AN: 151574 Hom.: 13270 Cov.: 31 AF XY: 0.419 AC XY: 31024 AN XY: 74046

African (AFR) AF: 0.419 AC: 17316 AN: 41356

American (AMR) AF: 0.414 AC: 6312 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1853 AN: 3470

East Asian (EAS) AF: 0.458 AC: 2366 AN: 5168

South Asian (SAS) AF: 0.490 AC: 2367 AN: 4828

European-Finnish (FIN) AF: 0.396 AC: 4098 AN: 10336

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27517 AN: 67856

Other (OTH) AF: 0.428 AC: 901 AN: 2106

Alfa AF: 0.418 Hom.: 53946

Bravo AF: 0.419

Asia WGS AF: 0.507 AC: 1760 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.75
PhyloP100		-1.4
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: rs1150739; hg19: chr6-30031345;