dbSNP rs10745: POLR1H:p.Gln101Gln (chr6-30062280-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81

Publications

22 publications found

Variant links:

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]

POLR1H links:

POLR1HASP (HGNC:):

POLR1HASP links:

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]

PPP1R11 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1H	NM_170783.4 link	c.303G>A	p.Gln101Gln	synonymous_variant	Exon 3 of 4	ENST00000332435.10	NP_740753.1	Q9P1U0Q2L6J2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR1H	ENST00000332435.10 link	c.303G>A	p.Gln101Gln	synonymous_variant	Exon 3 of 4	1	NM_170783.4	ENSP00000331111.5		Q9P1U0

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7898

AN:

152150

Hom.:

254

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0486

AC XY:

35318

AN XY:

726674

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

3476

6951

10427

13902

17378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1914

3828

5742

7656

9570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0520

AC:

7912

AN:

152268

Hom.:

255

Cov.:

AF XY:

0.0518

AC XY:

3855

AN XY:

74440

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0515

AC:

3502

AN:

68024

Other (OTH)

AF:

0.0587

AC:

124

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

399

798

1198

1597

1996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

3.8

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over