dbSNP rs3869066: POLR1HASP:n.438-4T>C (chr6-30035987-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 ENST00000420251.5(POLR1HASP):n.438-4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 456,638 control chromosomes in the GnomAD database, including 376 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 0.022 ( 71 hom., cov: 32)

Exomes 𝑓: 0.031 ( 305 hom. )

Consequence

POLR1HASP
ENST00000420251.5 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.196

Publications

9 publications found

Variant links:

Genes affected

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 ENST00000420251.5, 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=-1.03).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000420251.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1HASP	NR_026751.2		n.443-4T>C		splice_region intron	N/A
	POLR1HASP	NR_145416.1		n.443-4T>C		splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
POLR1HASP	ENST00000420251.5	TSL:1	n.438-4T>C	splice_region intron	N/A
POLR1HASP	ENST00000437417.5	TSL:1	n.977-4T>C	splice_region intron	N/A
POLR1HASP	ENST00000376797.7	TSL:2	n.260-4T>C	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3357

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00719

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0596

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.0316

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.0158

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0233

Gnomad OTH

AF:

0.0205

GnomAD2 exomes

AF:

0.0376

AC:

5144

AN:

136902

AF XY:

0.0344

show subpopulations

Gnomad AFR exome

AF:

0.00513

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.0214

Gnomad EAS exome

AF:

0.0244

Gnomad FIN exome

AF:

0.0166

Gnomad NFE exome

AF:

0.0217

Gnomad OTH exome

AF:

0.0320

GnomAD4 exome

AF:

0.0310

AC:

9436

AN:

304296

Hom.:

305

Cov.:

AF XY:

0.0291

AC XY:

5048

AN XY:

173280

show subpopulations

African (AFR)

AF:

0.00556

AC:

AN:

8626

American (AMR)

AF:

0.109

AC:

2963

AN:

27254

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

236

AN:

10790

East Asian (EAS)

AF:

0.0334

AC:

307

AN:

9204

South Asian (SAS)

AF:

0.0276

AC:

1650

AN:

59732

European-Finnish (FIN)

AF:

0.0181

AC:

232

AN:

12788

Middle Eastern (MID)

AF:

0.0119

AC:

AN:

2780

European-Non Finnish (NFE)

AF:

0.0226

AC:

3593

AN:

158888

Other (OTH)

AF:

0.0263

AC:

374

AN:

14234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

426

852

1278

1704

2130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0221

AC:

3365

AN:

152342

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1643

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00717

AC:

298

AN:

41576

American (AMR)

AF:

0.0597

AC:

914

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

AN:

3472

East Asian (EAS)

AF:

0.0316

AC:

164

AN:

5186

South Asian (SAS)

AF:

0.0222

AC:

107

AN:

4828

European-Finnish (FIN)

AF:

0.0158

AC:

168

AN:

10622

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0233

AC:

1587

AN:

68034

Other (OTH)

AF:

0.0203

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

166

331

497

662

828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0261

Hom.:

187

Bravo

AF:

0.0267

Asia WGS

AF:

0.0290

AC:

100

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.3

(source)

DANN

Benign

0.61

PhyloP100

-0.20

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