rs16896970

Variant names:

• chr6-30065140-A-G
• rs16896970
• ENST00000849686.1:n.170+1740T>C

Variant summary

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

The ENST00000849686.1(POLR1HASP):​n.170+1740T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 152,320 control chromosomes in the GnomAD database, including 364 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 0.052 (364 hom., cov: 32)
• Consequence: POLR1HASP ENST00000849686.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 4 publications found

Genes affected

POLR1HASP (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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1H	NM_170783.4	c.*443A>G		downstream_gene_variant		ENST00000332435.10	NP_740753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1H	ENST00000332435.10	c.*443A>G		downstream_gene_variant		1	NM_170783.4	ENSP00000331111.5

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7938 AN: 152202 Hom.: 363 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0411

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0598

Gnomad OTH AF: 0.0498

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

GnomAD4 genome AF: 0.0521 AC: 7936 AN: 152320 Hom.: 364 Cov.: 32 AF XY: 0.0546 AC XY: 4065 AN XY: 74488

African (AFR) AF: 0.0131 AC: 545 AN: 41590

American (AMR) AF: 0.0411 AC: 629 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 193 AN: 3472

East Asian (EAS) AF: 0.190 AC: 982 AN: 5178

South Asian (SAS) AF: 0.159 AC: 766 AN: 4820

European-Finnish (FIN) AF: 0.0513 AC: 545 AN: 10616

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0598 AC: 4065 AN: 68018

Other (OTH) AF: 0.0502 AC: 106 AN: 2112

Alfa AF: 0.0551 Hom.: 510

Bravo AF: 0.0475

Asia WGS AF: 0.157 AC: 543 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.50
PhyloP100		0.090

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16896970; hg19: chr6-30032917;