rs10745

Positions:

• chr6-30062280-G-A

Variant summary

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

The NM_170783.4(POLR1H):​c.303G>A​(p.Gln101=) variant causes a synonymous change. The variant allele was found at a frequency of 0.049 in 1,612,958 control chromosomes in the GnomAD database, including 2,395 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 (255 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2140 hom.)
• Consequence: POLR1H NM_170783.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

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=-0.49).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR1H	NM_170783.4	c.303G>A	p.Gln101=	synonymous_variant	3/4	ENST00000332435.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR1H	ENST00000332435.10	c.303G>A	p.Gln101=	synonymous_variant	3/4	1	NM_170783.4	P1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7898 AN: 152150 Hom.: 254 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0362

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0515

Gnomad OTH AF: 0.0598

GnomAD3 exomes AF: 0.0485 AC: 12002 AN: 247258 Hom.: 416 AF XY: 0.0482 AC XY: 6489 AN XY: 134662

Gnomad AFR exome AF: 0.0488

Gnomad AMR exome AF: 0.0442

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.0296

Gnomad SAS exome AF: 0.0243

Gnomad FIN exome AF: 0.0234

Gnomad NFE exome AF: 0.0539

Gnomad OTH exome AF: 0.0536

GnomAD4 exome AF: 0.0486 AC: 71061 AN: 1460690 Hom.: 2140 Cov.: 32 AF XY: 0.0486 AC XY: 35318 AN XY: 726674

Gnomad4 AFR exome AF: 0.0455

Gnomad4 AMR exome AF: 0.0480

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.0739

Gnomad4 SAS exome AF: 0.0242

Gnomad4 FIN exome AF: 0.0240

Gnomad4 NFE exome AF: 0.0479

Gnomad4 OTH exome AF: 0.0554

GnomAD4 genome AF: 0.0520 AC: 7912 AN: 152268 Hom.: 255 Cov.: 32 AF XY: 0.0518 AC XY: 3855 AN XY: 74440

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.0678

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.0363

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0515

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0585 Hom.: 304

Bravo AF: 0.0545

Asia WGS AF: 0.0360 AC: 126 AN: 3478

EpiCase AF: 0.0581

EpiControl AF: 0.0577

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10745; hg19: chr6-30030057; COSMIC: COSV60137967; COSMIC: COSV60137967;