chr6-30062280-G-A

Variant names:

• chr6-30062280-G-A
• rs10745
• NM_170783.4:c.303G>A

Variant summary

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

The NM_170783.4(POLR1H):​c.303G>A​(p.Gln101Gln) 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
• Publications: 22 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170783.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1H	NM_170783.4	MANE Select	c.303G>A	p.Gln101Gln	synonymous	Exon 3 of 4	NP_740753.1
	POLR1H	NM_001278785.2		c.303G>A	p.Gln101Gln	synonymous	Exon 4 of 5	NP_001265714.1
	POLR1H	NM_001278786.2		c.303G>A	p.Gln101Gln	synonymous	Exon 4 of 5	NP_001265715.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1H	ENST00000332435.10	TSL:1 MANE Select	c.303G>A	p.Gln101Gln	synonymous	Exon 3 of 4	ENSP00000331111.5
	POLR1H	ENST00000359374.8	TSL:1	c.303G>A	p.Gln101Gln	synonymous	Exon 4 of 5	ENSP00000352333.4
	POLR1H	ENST00000471008.5	TSL:1	n.3382G>A		non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes AF: 0.0485 AC: 12002 AN: 247258 AF XY: 0.0482

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 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

African (AFR) AF: 0.0455 AC: 1522 AN: 33478

American (AMR) AF: 0.0480 AC: 2145 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 4260 AN: 26134

East Asian (EAS) AF: 0.0739 AC: 2932 AN: 39700

South Asian (SAS) AF: 0.0242 AC: 2087 AN: 86258

European-Finnish (FIN) AF: 0.0240 AC: 1257 AN: 52316

Middle Eastern (MID) AF: 0.0463 AC: 267 AN: 5768

European-Non Finnish (NFE) AF: 0.0479 AC: 53244 AN: 1111932

Other (OTH) AF: 0.0554 AC: 3347 AN: 60380

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

African (AFR) AF: 0.0496 AC: 2062 AN: 41548

American (AMR) AF: 0.0678 AC: 1037 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 605 AN: 3472

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5178

South Asian (SAS) AF: 0.0234 AC: 113 AN: 4828

European-Finnish (FIN) AF: 0.0238 AC: 252 AN: 10608

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0515 AC: 3502 AN: 68024

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0574 Hom.: 819

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		3.8
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10745; hg19: chr6-30030057; COSMIC: COSV60137967; COSMIC: COSV60137967;