19-1611740-C-G
Variant names:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_003200.5(TCF3):āc.1932G>Cā(p.Leu644Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 31)
Exomes š: 0.000027 ( 0 hom. )
Consequence
TCF3
NM_003200.5 synonymous
NM_003200.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 19-1611740-C-G is Benign according to our data. Variant chr19-1611740-C-G is described in ClinVar as [Benign]. Clinvar id is 763988.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000526 (8/152176) while in subpopulation EAS AF= 0.00135 (7/5180). AF 95% confidence interval is 0.000634. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCF3 | ENST00000262965.12 | c.1932G>C | p.Leu644Leu | synonymous_variant | Exon 19 of 19 | 1 | NM_003200.5 | ENSP00000262965.5 | ||
TCF3 | ENST00000588136.7 | c.1923G>C | p.Leu641Leu | synonymous_variant | Exon 19 of 20 | 2 | NM_001136139.4 | ENSP00000468487.1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152058Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000192 AC: 48AN: 250462Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135644
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461502Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727064
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152176Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74410
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Nov 08, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at