dbSNP rs7758512: POLR1HASP:n.709-80A>C (chr6-30002812-T-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.709-80A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,414 control chromosomes in the GnomAD database, including 2,744 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 0.17 ( 2742 hom., cov: 32)

Exomes 𝑓: 0.16 ( 2 hom. )

Consequence

POLR1HASP
ENST00000420251.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

47 publications found

Variant links:

Genes affected

POLR1HASP (HGNC:):

POLR1HASP 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR1HASP	NR_026751.2 link	n.714-80A>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
POLR1HASP	ENST00000420251.5 link	n.709-80A>C	intron_variant	Intron 5 of 5	1
POLR1HASP	ENST00000376797.7 link	n.1549-80A>C	intron_variant	Intron 11 of 11	2
POLR1HASP	ENST00000422224.6 link	n.823-14585A>C	intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25911

AN:

152032

Hom.:

2725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.0475

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.193

GnomAD4 exome

AF:

0.163

AC:

AN:

264

Hom.:

AF XY:

0.149

AC XY:

AN XY:

168

show subpopulations

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.125

AC:

AN:

South Asian (SAS)

AF:

0.0714

AC:

AN:

European-Finnish (FIN)

AF:

0.133

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.148

AC:

AN:

162

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

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:

0.171

AC:

25963

AN:

152150

Hom.:

2742

Cov.:

AF XY:

0.169

AC XY:

12554

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.274

AC:

11388

AN:

41490

American (AMR)

AF:

0.211

AC:

3219

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1047

AN:

3464

East Asian (EAS)

AF:

0.189

AC:

976

AN:

5168

South Asian (SAS)

AF:

0.182

AC:

877

AN:

4820

European-Finnish (FIN)

AF:

0.0475

AC:

504

AN:

10610

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7461

AN:

67996

Other (OTH)

AF:

0.193

AC:

407

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1041

2081

3122

4162

5203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.145

Hom.:

4202

Bravo

AF:

0.191

Asia WGS

AF:

0.210

AC:

731

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.72

PhyloP100

-1.9

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