Variant chr19-1609670-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003200.5(TCF3):c.*2037A>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 0.246 in 222,518 control chromosomes in the GnomAD database, including 7,156 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 0.25 ( 4687 hom., cov: 30)

Exomes 𝑓: 0.24 ( 2469 hom. )

Consequence

TCF3
NM_003200.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.703

Variant links:

Genes affected

TCF3 (HGNC:11633): (transcription factor 3) This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and are inhibited by heterodimerization with inhibitor of DNA-binding (class IV) helix-loop-helix proteins. E proteins play a critical role in lymphopoiesis, and the encoded protein is required for B and T lymphocyte development. Deletion of this gene or diminished activity of the encoded protein may play a role in lymphoid malignancies. This gene is also involved in several chromosomal translocations that are associated with lymphoid malignancies including pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1), childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Sep 2011]

TCF3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF3	NM_003200.5 link	c.*2037A>G		3_prime_UTR_variant	19/19	ENST00000262965.12	NP_003191.1	P15923-1
TCF3	NM_001136139.4 link	c.*1703A>G		3_prime_UTR_variant	20/20	ENST00000588136.7	NP_001129611.1	P15923-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF3	ENST00000262965 link	c.*2037A>G		3_prime_UTR_variant	19/19	1	NM_003200.5	ENSP00000262965.5		P15923-1
TCF3	ENST00000588136 link	c.*1703A>G		3_prime_UTR_variant	20/20	2	NM_001136139.4	ENSP00000468487.1		P15923-2

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

36797

AN:

149048

Hom.:

4685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.145

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.244

AC:

17888

AN:

73342

Hom.:

2469

Cov.:

AF XY:

0.243

AC XY:

8268

AN XY:

34004

show subpopulations

Gnomad4 AFR exome

AF:

0.281

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.450

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.0926

Gnomad4 NFE exome

AF:

0.199

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.247

AC:

36832

AN:

149176

Hom.:

4687

Cov.:

AF XY:

0.251

AC XY:

18253

AN XY:

72814

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.230

Gnomad4 ASJ

AF:

0.250

Gnomad4 EAS

AF:

0.439

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.219

Alfa

AF:

0.194

Hom.:

2851

Bravo

AF:

0.244

Asia WGS

AF:

0.264

AC:

916

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.6

DANN

Benign

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over