Genetic Variant POLR1HASP:n.708+1998A>G (chr6-30032910-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000420251.5(POLR1HASP):n.708+1998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 1,025,662 control chromosomes in the GnomAD database, including 2,859 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 ( 364 hom., cov: 32)

Exomes 𝑓: 0.065 ( 2495 hom. )

Consequence

POLR1HASP
ENST00000420251.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.201

Publications

16 publications found

Variant links:

Genes affected

POLR1HASP (HGNC:):

POLR1HASP links:

ETF1P1 (HGNC:3478): (eukaryotic translation termination factor 1 pseudogene 1)

ETF1P1 links:

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

POLR1HASP 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=-0.63).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ETF1P1		n.30032910T>C	intragenic_variant
POLR1HASP	NR_026751.2 link	n.713+1998A>G	intron_variant	Intron 5 of 5
POLR1HASP	NR_145416.1 link	n.713+1998A>G	intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
POLR1HASP	ENST00000420251.5 link	n.708+1998A>G	intron_variant	Intron 5 of 5	1
POLR1HASP	ENST00000437417.5 link	n.1247+1998A>G	intron_variant	Intron 4 of 5	1
POLR1HASP	ENST00000444051.1 link	n.108+1998A>G	intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.0523

AC:

7952

AN:

152136

Hom.:

363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.0980

Gnomad AMR

AF:

0.0411

Gnomad ASJ

AF:

0.0556

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0515

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0597

Gnomad OTH

AF:

0.0501

GnomAD4 exome

AF:

0.0648

AC:

56568

AN:

873408

Hom.:

2495

Cov.:

AF XY:

0.0686

AC XY:

31185

AN XY:

454622

show subpopulations

African (AFR)

AF:

0.0102

AC:

219

AN:

21456

American (AMR)

AF:

0.0349

AC:

1230

AN:

35250

Ashkenazi Jewish (ASJ)

AF:

0.0569

AC:

1076

AN:

18910

East Asian (EAS)

AF:

0.122

AC:

4437

AN:

36466

South Asian (SAS)

AF:

0.149

AC:

9887

AN:

66560

European-Finnish (FIN)

AF:

0.0489

AC:

2393

AN:

48906

Middle Eastern (MID)

AF:

0.0592

AC:

161

AN:

2718

European-Non Finnish (NFE)

AF:

0.0573

AC:

34618

AN:

603766

Other (OTH)

AF:

0.0647

AC:

2547

AN:

39376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

2399

4799

7198

9598

11997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1010

2020

3030

4040

5050

<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:

0.0522

AC:

7950

AN:

152254

Hom.:

364

Cov.:

AF XY:

0.0547

AC XY:

4074

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0133

AC:

552

AN:

41564

American (AMR)

AF:

0.0411

AC:

628

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0556

AC:

193

AN:

3470

East Asian (EAS)

AF:

0.190

AC:

985

AN:

5172

South Asian (SAS)

AF:

0.160

AC:

771

AN:

4830

European-Finnish (FIN)

AF:

0.0515

AC:

545

AN:

10586

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0597

AC:

4064

AN:

68018

Other (OTH)

AF:

0.0506

AC:

107

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

387

773

1160

1546

1933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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:

0.0564

Hom.:

745

Bravo

AF:

0.0476

Asia WGS

AF:

0.158

AC:

548

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.4

(source)

DANN

Benign

0.63

PhyloP100

0.20

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over