Genetic Variant ENST00000607033.5:n.84G>A (chr6-133888899-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000607033.5(TARID):n.84G>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 0.61 in 177,714 control chromosomes in the GnomAD database, including 34,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.60 ( 28638 hom., cov: 32)

Exomes 𝑓: 0.67 ( 6068 hom. )

Consequence

TARID
ENST00000607033.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.468

Publications

7 publications found

Variant links:

COSMIC-nc: COSV52819538

Genes affected

TARID (HGNC:50506): (TCF21 antisense RNA inducing promoter demethylation)

TARID links:

TCF21 (HGNC:11632): (transcription factor 21) TCF21 encodes a transcription factor of the basic helix-loop-helix family. The TCF21 product is mesoderm specific, and expressed in embryonic epicardium, mesenchyme-derived tissues of lung, gut, gonad, and both mesenchymal and glomerular epithelial cells in the kidney. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

TCF21 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

TCF21 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000607033.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 6-133888899-C-T is Benign according to our data. Variant chr6-133888899-C-T is described in ClinVar as Benign. ClinVar VariationId is 1278224.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000607033.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TARID	NR_109982.1		n.108G>A	non_coding_transcript_exon	Exon 1 of 9
TCF21	NM_003206.4	MANE Select	c.-499C>T	upstream_gene	N/A	NP_003197.2
TCF21	NM_198392.3		c.-499C>T	upstream_gene	N/A	NP_938206.1	O43680

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
TARID	ENST00000607033.5	TSL:1	n.84G>A	non_coding_transcript_exon	Exon 1 of 9
TARID	ENST00000607641.3	TSL:1	n.1430G>A	non_coding_transcript_exon	Exon 2 of 3
TARID	ENST00000630728.1	TSL:1	n.1648G>A	non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91141

AN:

151940

Hom.:

28620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.430

Gnomad AMI

AF:

0.695

Gnomad AMR

AF:

0.729

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.926

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.653

Gnomad OTH

AF:

0.612

GnomAD4 exome

AF:

0.669

AC:

17152

AN:

25654

Hom.:

6068

Cov.:

AF XY:

0.673

AC XY:

8859

AN XY:

13156

show subpopulations

African (AFR)

AF:

0.424

AC:

174

AN:

410

American (AMR)

AF:

0.775

AC:

2442

AN:

3152

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

190

AN:

316

East Asian (EAS)

AF:

0.934

AC:

1406

AN:

1506

South Asian (SAS)

AF:

0.728

AC:

2214

AN:

3042

European-Finnish (FIN)

AF:

0.493

AC:

364

AN:

738

Middle Eastern (MID)

AF:

0.568

AC:

AN:

European-Non Finnish (NFE)

AF:

0.631

AC:

9565

AN:

15170

Other (OTH)

AF:

0.606

AC:

755

AN:

1246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

252

505

757

1010

1262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<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:

0.600

AC:

91201

AN:

152060

Hom.:

28638

Cov.:

AF XY:

0.600

AC XY:

44560

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.430

AC:

17826

AN:

41460

American (AMR)

AF:

0.729

AC:

11152

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.642

AC:

2225

AN:

3466

East Asian (EAS)

AF:

0.926

AC:

4798

AN:

5180

South Asian (SAS)

AF:

0.715

AC:

3441

AN:

4814

European-Finnish (FIN)

AF:

0.500

AC:

5275

AN:

10560

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.653

AC:

44376

AN:

67972

Other (OTH)

AF:

0.615

AC:

1300

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1757

3513

5270

7026

8783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.651

Hom.:

54184

Bravo

AF:

0.612

Asia WGS

AF:

0.764

AC:

2656

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.4

(source)

DANN

Benign

0.59

PhyloP100

-0.47

PromoterAI

0.055

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over