rs7769930

Variant names:

• chr6-30061030-A-C
• rs7769930
• ENST00000437417.5:n.611T>G

Variant summary

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

The XM_047418695.1(POLR1H):​c.-10-485A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 153,862 control chromosomes in the GnomAD database, including 2,242 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 0.15 (2235 hom., cov: 33)
  • Exomes 𝑓: 0.074 (7 hom.)
• Consequence: POLR1H XM_047418695.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352

Genes affected

POLR1HASP (HGNC:13924): (POLR1H antisense, pseudogene)

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]

ENSG00000278773 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1H	NM_170783.4	c.-495A>C		upstream_gene_variant		ENST00000332435.10	NP_740753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1H	ENST00000332435.10	c.-495A>C		upstream_gene_variant		1	NM_170783.4	ENSP00000331111.5

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22505 AN: 152114 Hom.: 2225 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.0742 AC: 121 AN: 1630 Hom.: 7 Cov.: 0 AF XY: 0.0831 AC XY: 72 AN XY: 866

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.0924

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0540

Gnomad4 OTH exome AF: 0.0333

GnomAD4 genome AF: 0.148 AC: 22543 AN: 152232 Hom.: 2235 Cov.: 33 AF XY: 0.146 AC XY: 10883 AN XY: 74454

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0861

Gnomad4 OTH AF: 0.168

Alfa AF: 0.116 Hom.: 535

Bravo AF: 0.164

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.7
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7769930; hg19: chr6-30028807;