Genetic Variant POLR1HASP:n.589-3409A>C (chr6-29950325-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000849678.1(POLR1HASP):n.589-3409A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0035 ( 0 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

POLR1HASP
ENST00000849678.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.89

Publications

2 publications found

Variant links:

Genes affected

POLR1HASP (HGNC:):

POLR1HASP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
POLR1HASP	ENST00000849678.1 link	n.589-3409A>C	intron_variant	Intron 3 of 4
POLR1HASP	ENST00000849679.1 link	n.66-21779A>C	intron_variant	Intron 1 of 5
POLR1HASP	ENST00000849682.1 link	n.751-21779A>C	intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.00352

AC:

497

AN:

141134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00835

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00503

Gnomad ASJ

AF:

0.00156

Gnomad EAS

AF:

0.00604

Gnomad SAS

AF:

0.00820

Gnomad FIN

AF:

0.000287

Gnomad MID

AF:

0.00352

Gnomad NFE

AF:

0.000734

Gnomad OTH

AF:

0.00261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00354

AC:

500

AN:

141228

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

231

AN XY:

69240

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00832

AC:

301

AN:

36178

American (AMR)

AF:

0.00517

AC:

AN:

13936

Ashkenazi Jewish (ASJ)

AF:

0.00156

AC:

AN:

3196

East Asian (EAS)

AF:

0.00606

AC:

AN:

4620

South Asian (SAS)

AF:

0.00844

AC:

AN:

4386

European-Finnish (FIN)

AF:

0.000287

AC:

AN:

10454

Middle Eastern (MID)

AF:

0.00379

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.000734

AC:

AN:

65360

Other (OTH)

AF:

0.00260

AC:

AN:

1926

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.282

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00110

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.6

(source)

DANN

Benign

0.26

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over