Genetic Variant TRD-AS1:n.207C>A (chr14-22481259-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000514473.2(TRD-AS1):n.207C>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 0.118 in 151,504 control chromosomes in the GnomAD database, including 1,598 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 0.12 ( 1596 hom., cov: 27)

Exomes 𝑓: 0.27 ( 2 hom. )

Consequence

TRD-AS1
ENST00000514473.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.174

Publications

7 publications found

Variant links:

COSMIC-nc: COSV66606808

Genes affected

TRD-AS1 (HGNC:56197): (TRD antisense RNA 1)

TRD-AS1 links:

TRA (HGNC:12027):

TRA 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=-0.51).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRD-AS1	NR_148361.1 link	n.207C>A		non_coding_transcript_exon_variant	Exon 2 of 5
TRA		n.22481259G>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRD-AS1	ENST00000514473.2 link	n.207C>A		non_coding_transcript_exon_variant	Exon 2 of 3	2
TRD-AS1	ENST00000556777.2 link	n.544C>A		non_coding_transcript_exon_variant	Exon 2 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17926

AN:

151364

Hom.:

1595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0492

Gnomad AMI

AF:

0.200

Gnomad AMR

AF:

0.0885

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.485

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.124

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.108

GnomAD4 exome

AF:

0.273

AC:

AN:

Hom.:

Cov.:

AF XY:

0.188

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)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.188

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: 0.300

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.118

AC:

17915

AN:

151482

Hom.:

1596

Cov.:

AF XY:

0.123

AC XY:

9121

AN XY:

74040

show subpopulations

African (AFR)

AF:

0.0491

AC:

2025

AN:

41224

American (AMR)

AF:

0.0883

AC:

1341

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

394

AN:

3466

East Asian (EAS)

AF:

0.485

AC:

2502

AN:

5156

South Asian (SAS)

AF:

0.231

AC:

1110

AN:

4796

European-Finnish (FIN)

AF:

0.174

AC:

1819

AN:

10474

Middle Eastern (MID)

AF:

0.123

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.122

AC:

8281

AN:

67884

Other (OTH)

AF:

0.107

AC:

226

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

738

1476

2214

2952

3690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

218

436

654

872

1090

<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:

0.120

Hom.:

2305

Bravo

AF:

0.108

Asia WGS

AF:

0.318

AC:

1106

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.17

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