Genetic Variant TCF21:c.*241C>G (chr6-133893387-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000237316.3(TCF21):c.*241C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,186 control chromosomes in the GnomAD database, including 8,820 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 0.31 ( 8812 hom., cov: 33)

Exomes 𝑓: 0.38 ( 8 hom. )

Consequence

TCF21
ENST00000237316.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.704

Publications

168 publications found

Variant links:

Genes affected

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 links:

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

TARID 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=-0.79).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF21	NM_198392.3 link	c.*241C>G		3_prime_UTR_variant	Exon 3 of 3		NP_938206.1	O43680

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TCF21	ENST00000237316.3 link	c.*241C>G	3_prime_UTR_variant	Exon 3 of 3	1	ENSP00000237316.3	O43680
TARID	ENST00000795402.1 link	n.151+23675G>C	intron_variant	Intron 1 of 5
TARID	ENST00000795414.1 link	n.208+23675G>C	intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47160

AN:

151982

Hom.:

8802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0893

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.406

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.331

GnomAD4 exome

AF:

0.375

AC:

AN:

Hom.:

Cov.:

AF XY:

0.381

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.417

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.292

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.310

AC:

47172

AN:

152098

Hom.:

8812

Cov.:

AF XY:

0.321

AC XY:

23836

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0890

AC:

3697

AN:

41526

American (AMR)

AF:

0.411

AC:

6277

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

1409

AN:

3472

East Asian (EAS)

AF:

0.421

AC:

2169

AN:

5150

South Asian (SAS)

AF:

0.503

AC:

2426

AN:

4822

European-Finnish (FIN)

AF:

0.462

AC:

4876

AN:

10558

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.370

AC:

25154

AN:

67966

Other (OTH)

AF:

0.335

AC:

706

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1561

3123

4684

6246

7807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.229

Hom.:

621

Bravo

AF:

0.296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.7

(source)

DANN

Benign

0.67

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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