rs11752321

Positions:

• chr6-30064542-G-C

Variant summary

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

The NM_170783.4(POLR1H):​c.357-131G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 685,642 control chromosomes in the GnomAD database, including 446 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 0.025 (118 hom., cov: 32)
  • Exomes 𝑓: 0.016 (328 hom.)
• Consequence: POLR1H NM_170783.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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:):

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 (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1H	NM_170783.4	c.357-131G>C		intron_variant		ENST00000332435.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1H	ENST00000332435.10	c.357-131G>C		intron_variant		1	NM_170783.4	P1

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3849 AN: 151928 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.0529

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.0887

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.000948

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00569

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.0159 AC: 8468 AN: 533596 Hom.: 328 AF XY: 0.0178 AC XY: 4979 AN XY: 279256

Gnomad4 AFR exome AF: 0.0468

Gnomad4 AMR exome AF: 0.00776

Gnomad4 ASJ exome AF: 0.00483

Gnomad4 EAS exome AF: 0.0885

Gnomad4 SAS exome AF: 0.0788

Gnomad4 FIN exome AF: 0.00163

Gnomad4 NFE exome AF: 0.00445

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.0254 AC: 3858 AN: 152046 Hom.: 118 Cov.: 32 AF XY: 0.0265 AC XY: 1971 AN XY: 74324

Gnomad4 AFR AF: 0.0529

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.0887

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.000948

Gnomad4 NFE AF: 0.00569

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0154 Hom.: 10

Bravo AF: 0.0261

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs11752321; hg19: chr6-30032319;