Genetic Variant ENST00000420251.5:n.709-3416G>A (chr6-30006148-C-T) – 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.709-3416G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 188,392 control chromosomes in the GnomAD database, including 58,914 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 0.78 ( 46622 hom., cov: 32)

Exomes 𝑓: 0.82 ( 12292 hom. )

Consequence

POLR1HASP
ENST00000420251.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.454

Publications

38 publications found

Variant links:

Genes affected

POLR1HASP (HGNC:):

POLR1HASP links:

HLA-J (HGNC:4967): (major histocompatibility complex, class I, J (pseudogene)) This major histocompatibility complex gene represents a transcribed pseudogene, possibly derived from HLA-A. [provided by RefSeq, May 2010]

HLA-J 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-J	NR_024240.1 link	n.169+9C>T		intron_variant	Intron 1 of 6
POLR1HASP	NR_026751.2 link	n.714-3416G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
POLR1HASP	ENST00000420251.5 link	n.709-3416G>A	intron_variant	Intron 5 of 5	1
ENSG00000237669	ENST00000458060.1 link	n.969G>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
POLR1HASP	ENST00000849694.1 link	n.1816G>A	non_coding_transcript_exon_variant	Exon 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.780

AC:

118574

AN:

151942

Hom.:

46584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.695

Gnomad AMI

AF:

0.935

Gnomad AMR

AF:

0.775

Gnomad ASJ

AF:

0.780

Gnomad EAS

AF:

0.838

Gnomad SAS

AF:

0.788

Gnomad FIN

AF:

0.866

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.814

Gnomad OTH

AF:

0.761

GnomAD4 exome

AF:

0.816

AC:

29655

AN:

36332

Hom.:

12292

Cov.:

AF XY:

0.818

AC XY:

15161

AN XY:

18530

show subpopulations

African (AFR)

AF:

0.745

AC:

152

AN:

204

American (AMR)

AF:

0.751

AC:

771

AN:

1026

Ashkenazi Jewish (ASJ)

AF:

0.776

AC:

559

AN:

720

East Asian (EAS)

AF:

0.841

AC:

222

AN:

264

South Asian (SAS)

AF:

0.814

AC:

3965

AN:

4870

European-Finnish (FIN)

AF:

0.840

AC:

1473

AN:

1754

Middle Eastern (MID)

AF:

0.832

AC:

213

AN:

256

European-Non Finnish (NFE)

AF:

0.821

AC:

20480

AN:

24934

Other (OTH)

AF:

0.790

AC:

1820

AN:

2304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

251

502

754

1005

1256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.780

AC:

118664

AN:

152060

Hom.:

46622

Cov.:

AF XY:

0.783

AC XY:

58209

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.695

AC:

28799

AN:

41456

American (AMR)

AF:

0.775

AC:

11842

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.780

AC:

2704

AN:

3468

East Asian (EAS)

AF:

0.838

AC:

4327

AN:

5166

South Asian (SAS)

AF:

0.787

AC:

3790

AN:

4814

European-Finnish (FIN)

AF:

0.866

AC:

9177

AN:

10592

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.814

AC:

55342

AN:

67970

Other (OTH)

AF:

0.764

AC:

1613

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1282

2564

3846

5128

6410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<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:

0.795

Hom.:

69673

Bravo

AF:

0.767

Asia WGS

AF:

0.817

AC:

2840

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.3

(source)

DANN

Benign

0.65

PhyloP100

-0.45

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