rs16896970

Variant names:

• chr6-30065140-A-G
• rs16896970
• XM_047419279.1:c.-552-1719A>G

Variant summary

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

The XM_047419279.1(PPP1R11):​c.-552-1719A>G 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: PPP1R11 XM_047419279.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

Genes affected

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

Verdict is Benign. Variant got -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

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.0411

Gnomad4 ASJ AF: 0.0556

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.0598

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0523 Hom.: 65

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16896970; hg19: chr6-30032917;