rs41275834

Positions:

• chr19-1609617-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000262965.12(TCF3):​c.*2090T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 221,084 control chromosomes in the GnomAD database, including 1,235 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 0.029 (476 hom., cov: 31)
  • Exomes 𝑓: 0.067 (759 hom.)
• Consequence: TCF3 ENST00000262965.12 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF3	NM_001136139.4	c.*1756T>A		3_prime_UTR_variant	20/20	ENST00000588136.7	NP_001129611.1
TCF3	NM_003200.5	c.*2090T>A		3_prime_UTR_variant	19/19	ENST00000262965.12	NP_003191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF3	ENST00000262965.12	c.*2090T>A		3_prime_UTR_variant	19/19	1	NM_003200.5	ENSP00000262965	A1
TCF3	ENST00000588136.7	c.*1756T>A		3_prime_UTR_variant	20/20	2	NM_001136139.4	ENSP00000468487	P3

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4420 AN: 151748 Hom.: 478 Cov.: 31

Gnomad AFR AF: 0.00525

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.00492

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00503

Gnomad OTH AF: 0.0316

GnomAD4 exome AF: 0.0669 AC: 4633 AN: 69218 Hom.: 759 Cov.: 0 AF XY: 0.0659 AC XY: 2109 AN XY: 32002

Gnomad4 AFR exome AF: 0.00379

Gnomad4 AMR exome AF: 0.0710

Gnomad4 ASJ exome AF: 0.0461

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.0623

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00551

Gnomad4 OTH exome AF: 0.0320

GnomAD4 genome AF: 0.0291 AC: 4416 AN: 151866 Hom.: 476 Cov.: 31 AF XY: 0.0336 AC XY: 2491 AN XY: 74238

Gnomad4 AFR AF: 0.00524

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.0758

Gnomad4 FIN AF: 0.00492

Gnomad4 NFE AF: 0.00503

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0120 Hom.: 12

Bravo AF: 0.0348

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs41275834; hg19: chr19-1609616;