dbSNP rs3188482: POLR1H:n.3659A>G (chr6-30064896-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000471008.5(POLR1H):n.3659A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 433,336 control chromosomes in the GnomAD database, including 2,756 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 0.12 ( 1505 hom., cov: 32)

Exomes 𝑓: 0.078 ( 1251 hom. )

Consequence

POLR1H
ENST00000471008.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.436

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:

Genome browser will be placed here

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=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1H	NM_170783.4 link	c.*199A>G		3_prime_UTR_variant	Exon 4 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.*199A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_170783.4	ENSP00000331111.5		Q9P1U0

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17941

AN:

152072

Hom.:

1496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0238

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0579

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.0784

AC:

22047

AN:

281146

Hom.:

1251

Cov.:

AF XY:

0.0774

AC XY:

11267

AN XY:

145608

show subpopulations

African (AFR)

AF:

0.223

AC:

1688

AN:

7584

American (AMR)

AF:

0.152

AC:

1213

AN:

7970

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

1231

AN:

9960

East Asian (EAS)

AF:

0.165

AC:

3828

AN:

23144

South Asian (SAS)

AF:

0.120

AC:

1457

AN:

12160

European-Finnish (FIN)

AF:

0.0266

AC:

596

AN:

22404

Middle Eastern (MID)

AF:

0.124

AC:

232

AN:

1870

European-Non Finnish (NFE)

AF:

0.0565

AC:

10053

AN:

178044

Other (OTH)

AF:

0.0971

AC:

1749

AN:

18010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

911

1822

2734

3645

4556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.118

AC:

17973

AN:

152190

Hom.:

1505

Cov.:

AF XY:

0.116

AC XY:

8657

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.225

AC:

9311

AN:

41466

American (AMR)

AF:

0.141

AC:

2163

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

445

AN:

3470

East Asian (EAS)

AF:

0.149

AC:

772

AN:

5190

South Asian (SAS)

AF:

0.158

AC:

763

AN:

4816

European-Finnish (FIN)

AF:

0.0238

AC:

253

AN:

10618

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0579

AC:

3936

AN:

68018

Other (OTH)

AF:

0.130

AC:

275

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

771

1542

2314

3085

3856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.0826

Hom.:

2786

Bravo

AF:

0.136

Asia WGS

AF:

0.145

AC:

505

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

2.3

(source)

DANN

Benign

0.86

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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