Genetic Variant ENSG00000291066:n.454G>A (chr16-21818699-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000551681.3(ENSG00000291066):n.454G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.000226 in 1,607,190 control chromosomes in the GnomAD database, including 5 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 0.00026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 5 hom. )

Consequence

ENSG00000291066
ENST00000551681.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.52

Publications

1 publications found

Variant links:

Genes affected

ENSG00000291066 (HGNC:):

ENSG00000291066 links:

RRN3P1 (HGNC:30548): (RRN3 pseudogene 1) Predicted to enable RNA polymerase I core binding activity and RNA polymerase I general transcription initiation factor activity. Predicted to be involved in transcription initiation from RNA polymerase I promoter. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RRN3P1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRN3P1	NR_003370.2 link	n.129G>A		non_coding_transcript_exon_variant	Exon 2 of 12

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000291066	ENST00000551681.3 link	n.454G>A	non_coding_transcript_exon_variant	Exon 3 of 8	1
RRN3P1	ENST00000551901.6 link	n.153G>A	non_coding_transcript_exon_variant	Exon 2 of 13	6
ENSG00000291066	ENST00000685193.2 link	n.596G>A	non_coding_transcript_exon_variant	Exon 3 of 13

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00519

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000958

GnomAD4 exome

AF:

0.000223

AC:

324

AN:

1454952

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

230

AN XY:

724248

show subpopulations

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

African (AFR)

AF:

0.0000300

AC:

AN:

33310

American (AMR)

AF:

0.0000224

AC:

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.000227

AC:

AN:

39654

South Asian (SAS)

AF:

0.00283

AC:

243

AN:

85868

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000443

AC:

AN:

1106060

Other (OTH)

AF:

0.000316

AC:

AN:

60126

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.364

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000256

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41554

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000385

AC:

AN:

5194

South Asian (SAS)

AF:

0.00540

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

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:

0.000324

Hom.:

Bravo

AF:

0.000136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

5.5

Mutation Taster

=84/16

polymorphism

(source)

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