dbSNP rs3757328: POLR1H:n.1677G>A (chr6-30060575-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 ENST00000471008.5(POLR1H):n.1677G>A 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 0.0961 in 152,166 control chromosomes in the GnomAD database, including 1,203 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 0.096 ( 1203 hom., cov: 32)

Exomes 𝑓: 0.031 ( 0 hom. )

Consequence

POLR1H
ENST00000471008.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.300

Publications

25 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:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
POLR1HASP	NR_026751.2 link	n.366+166C>T	intron_variant	Intron 2 of 5
POLR1HASP	NR_145416.1 link	n.366+166C>T	intron_variant	Intron 2 of 6
POLR1HASP	NR_145418.1 link	n.111+504C>T	intron_variant	Intron 1 of 2
POLR1H	XM_047418695.1 link	c.-11+498G>A	intron_variant	Intron 1 of 4	XP_047274651.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
POLR1H	ENST00000471008.5 link	n.1677G>A	non_coding_transcript_exon_variant	Exon 1 of 2	1
POLR1HASP	ENST00000420251.5 link	n.361+166C>T	intron_variant	Intron 2 of 5	1
POLR1HASP	ENST00000431012.5 link	n.101+504C>T	intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.0960

AC:

14592

AN:

152016

Hom.:

1197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0822

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.00811

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.111

GnomAD4 exome

AF:

0.0313

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0357

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0961

AC:

14616

AN:

152134

Hom.:

1203

Cov.:

AF XY:

0.0944

AC XY:

7025

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.217

AC:

9009

AN:

41460

American (AMR)

AF:

0.0821

AC:

1256

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

372

AN:

3470

East Asian (EAS)

AF:

0.118

AC:

609

AN:

5172

South Asian (SAS)

AF:

0.136

AC:

657

AN:

4818

European-Finnish (FIN)

AF:

0.00811

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0346

AC:

2351

AN:

68000

Other (OTH)

AF:

0.109

AC:

231

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

597

1194

1792

2389

2986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0599

Hom.:

1332

Bravo

AF:

0.109

Asia WGS

AF:

0.115

AC:

402

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.3

(source)

DANN

Benign

0.64

PhyloP100

-0.30

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over