19-1650135-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003200.5(TCF3):c.72+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,515,796 control chromosomes in the GnomAD database, including 183,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27521 hom., cov: 32)

Exomes 𝑓: 0.46 ( 155861 hom. )

Consequence

TCF3
NM_003200.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 19-1650135-A-G is Benign according to our data. Variant chr19-1650135-A-G is described in ClinVar as [Benign]. Clinvar id is 1185424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF3	NM_003200.5 link	c.72+42T>C		intron_variant	Intron 2 of 18	ENST00000262965.12	NP_003191.1	P15923-1
TCF3	NM_001136139.4 link	c.72+42T>C		intron_variant	Intron 2 of 19	ENST00000588136.7	NP_001129611.1	P15923-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF3	ENST00000262965.12 link	c.72+42T>C		intron_variant	Intron 2 of 18	1	NM_003200.5	ENSP00000262965.5		P15923-1
TCF3	ENST00000588136.7 link	c.72+42T>C		intron_variant	Intron 2 of 19	2	NM_001136139.4	ENSP00000468487.1		P15923-2

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86587

AN:

151790

Hom.:

27479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.829

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.582

Gnomad ASJ

AF:

0.405

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.718

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.532

GnomAD3 exomes

AF:

0.541

AC:

81014

AN:

149844

Hom.:

24617

AF XY:

0.543

AC XY:

43388

AN XY:

79958

show subpopulations

Gnomad AFR exome

AF:

0.839

Gnomad AMR exome

AF:

0.631

Gnomad ASJ exome

AF:

0.397

Gnomad EAS exome

AF:

0.869

Gnomad SAS exome

AF:

0.703

Gnomad FIN exome

AF:

0.337

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.484

GnomAD4 exome

AF:

0.461

AC:

628144

AN:

1363888

Hom.:

155861

Cov.:

AF XY:

0.466

AC XY:

314227

AN XY:

674408

show subpopulations

Gnomad4 AFR exome

AF:

0.845

Gnomad4 AMR exome

AF:

0.627

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.903

Gnomad4 SAS exome

AF:

0.700

Gnomad4 FIN exome

AF:

0.378

Gnomad4 NFE exome

AF:

0.413

Gnomad4 OTH exome

AF:

0.494

GnomAD4 genome

AF:

0.571

AC:

86686

AN:

151908

Hom.:

27521

Cov.:

AF XY:

0.576

AC XY:

42813

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.830

Gnomad4 AMR

AF:

0.582

Gnomad4 ASJ

AF:

0.405

Gnomad4 EAS

AF:

0.889

Gnomad4 SAS

AF:

0.716

Gnomad4 FIN

AF:

0.418

Gnomad4 NFE

AF:

0.413

Gnomad4 OTH

AF:

0.530

Alfa

AF:

0.438

Hom.:

20112

Bravo

AF:

0.593

Asia WGS

AF:

0.785

AC:

2727

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Agammaglobulinemia 8, autosomal dominant

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.3

DANN

Benign

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over