dbSNP rs7284767: TUG1:n.1075G>A (chr22-30973338-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000519077.4(TUG1):n.1075G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,998 control chromosomes in the GnomAD database, including 13,463 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 0.40 ( 13462 hom., cov: 32)

Exomes 𝑓: 0.75 ( 1 hom. )

Consequence

TUG1
ENST00000519077.4 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0280

Publications

12 publications found

Variant links:

Genes affected

TUG1 (HGNC:26066): (taurine up-regulated 1) Predicted to act upstream of or within photoreceptor cell development and regulation of gene expression. Predicted to be active in nucleus. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

TUG1 links:

ENSG00000275307 (HGNC:):

ENSG00000275307 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=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
TUG1	NR_152867.2 link	n.731G>A	non_coding_transcript_exon_variant	Exon 3 of 4
TUG1	NR_152868.2 link	n.731G>A	non_coding_transcript_exon_variant	Exon 3 of 4
TUG1	NM_001396518.1 link	c.*2445G>A	3_prime_UTR_variant	Exon 2 of 3	NP_001383447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUG1	ENST00000644773.3 link	c.*2445G>A		3_prime_UTR_variant	Exon 2 of 3			ENSP00000501406.2		A0A6I8PU40

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61365

AN:

151876

Hom.:

13444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.659

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.379

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ 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: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.404

AC:

61423

AN:

151994

Hom.:

13462

Cov.:

AF XY:

0.403

AC XY:

29952

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.557

AC:

23068

AN:

41422

American (AMR)

AF:

0.363

AC:

5551

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1141

AN:

3466

East Asian (EAS)

AF:

0.659

AC:

3412

AN:

5178

South Asian (SAS)

AF:

0.297

AC:

1429

AN:

4810

European-Finnish (FIN)

AF:

0.331

AC:

3495

AN:

10564

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.326

AC:

22177

AN:

67946

Other (OTH)

AF:

0.375

AC:

793

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1798

3596

5395

7193

8991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.356

Hom.:

2430

Bravo

AF:

0.413

Asia WGS

AF:

0.465

AC:

1617

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.8

(source)

DANN

Benign

0.70

PhyloP100

0.028

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