Genetic Variant TCF21:c.*469A>T (chr6-133893615-A-T) – 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.*469A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 152,254 control chromosomes in the GnomAD database, including 67,182 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 0.94 ( 67175 hom., cov: 32)

Exomes 𝑓: 0.94 ( 7 hom. )

Consequence

TCF21
ENST00000237316.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.550

Publications

12 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:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000237316.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF21	NM_198392.3		c.*469A>T		3_prime_UTR	Exon 3 of 3	NP_938206.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TCF21	ENST00000237316.3	TSL:1	c.*469A>T	3_prime_UTR	Exon 3 of 3	ENSP00000237316.3
TARID	ENST00000795402.1		n.151+23447T>A	intron	N/A
TARID	ENST00000795414.1		n.208+23447T>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.939

AC:

142813

AN:

152120

Hom.:

67114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.983

Gnomad AMI

AF:

0.897

Gnomad AMR

AF:

0.960

Gnomad ASJ

AF:

0.896

Gnomad EAS

AF:

0.886

Gnomad SAS

AF:

0.929

Gnomad FIN

AF:

0.902

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.920

Gnomad OTH

AF:

0.940

GnomAD4 exome

AF:

0.938

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

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)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.875

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: 0.275

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:

0.939

AC:

142933

AN:

152238

Hom.:

67175

Cov.:

AF XY:

0.938

AC XY:

69806

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.983

AC:

40842

AN:

41554

American (AMR)

AF:

0.960

AC:

14699

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.896

AC:

3110

AN:

3470

East Asian (EAS)

AF:

0.886

AC:

4587

AN:

5178

South Asian (SAS)

AF:

0.930

AC:

4473

AN:

4812

European-Finnish (FIN)

AF:

0.902

AC:

9542

AN:

10576

Middle Eastern (MID)

AF:

0.922

AC:

271

AN:

294

European-Non Finnish (NFE)

AF:

0.920

AC:

62607

AN:

68024

Other (OTH)

AF:

0.940

AC:

1984

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

455

910

1366

1821

2276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.926

Hom.:

8117

Bravo

AF:

0.947

Asia WGS

AF:

0.934

AC:

3248

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.4

(source)

DANN

Benign

0.47

PhyloP100

-0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over