dbSNP rs3757329: POLR1H:n.1749A>C (chr6-30060647-A-C) – 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.1749A>C 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 0.149 in 152,146 control chromosomes in the GnomAD database, including 2,249 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 0.15 ( 2247 hom., cov: 32)

Exomes 𝑓: 0.17 ( 2 hom. )

Consequence

POLR1H
ENST00000471008.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.654

Publications

18 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:

POLR1HASP (HGNC:13924): (POLR1H antisense, pseudogene)

POLR1HASP links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000471008.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471008.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
POLR1HASP	NR_026751.2	n.366+94T>G	intron	N/A
POLR1HASP	NR_145416.1	n.366+94T>G	intron	N/A
POLR1HASP	NR_145418.1	n.111+432T>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
POLR1H	ENST00000471008.5	TSL:1	n.1749A>C	non_coding_transcript_exon	Exon 1 of 2
POLR1HASP	ENST00000420251.5	TSL:1	n.361+94T>G	intron	N/A
POLR1HASP	ENST00000431012.5	TSL:1	n.101+432T>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22533

AN:

151926

Hom.:

2236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.0319

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.0862

Gnomad OTH

AF:

0.174

GnomAD4 exome

AF:

0.167

AC:

AN:

102

Hom.:

Cov.:

AF XY:

0.154

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.167

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.171

AC:

AN:

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.148

AC:

22577

AN:

152044

Hom.:

2247

Cov.:

AF XY:

0.146

AC XY:

10890

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.267

AC:

11078

AN:

41426

American (AMR)

AF:

0.151

AC:

2305

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

976

AN:

3470

East Asian (EAS)

AF:

0.157

AC:

808

AN:

5154

South Asian (SAS)

AF:

0.160

AC:

771

AN:

4810

European-Finnish (FIN)

AF:

0.0319

AC:

338

AN:

10600

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0862

AC:

5862

AN:

67974

Other (OTH)

AF:

0.173

AC:

365

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

921

1841

2762

3682

4603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.116

Hom.:

3472

Bravo

AF:

0.164

Asia WGS

AF:

0.182

AC:

632

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.6

(source)

DANN

Benign

0.77

PhyloP100

-0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over