rs201725633

chr19-1622040-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003200.5(TCF3):c.822+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,599,030 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (2 hom.)
• Consequence: TCF3 NM_003200.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.67

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-1622040-G-A is Benign according to our data. Variant chr19-1622040-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF3	NM_001136139.4	c.822+14C>T		intron_variant		ENST00000588136.7
TCF3	NM_003200.5	c.822+14C>T		intron_variant		ENST00000262965.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF3	ENST00000262965.12	c.822+14C>T		intron_variant		1	NM_003200.5	A1
TCF3	ENST00000588136.7	c.822+14C>T		intron_variant		2	NM_001136139.4	P3

Frequencies

GnomAD3 genomes AF: 0.000717 AC: 109 AN: 151938 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000927

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00108 AC: 233 AN: 214930 Hom.: 2 AF XY: 0.00107 AC XY: 126 AN XY: 117706

Gnomad AFR exome AF: 0.0000812

Gnomad AMR exome AF: 0.000714

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00450

Gnomad NFE exome AF: 0.00127

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.000883 AC: 1277 AN: 1446974 Hom.: 2 Cov.: 58 AF XY: 0.000837 AC XY: 601 AN XY: 718328

Gnomad4 AFR exome AF: 0.0000601

Gnomad4 AMR exome AF: 0.000695

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00427

Gnomad4 NFE exome AF: 0.000889

Gnomad4 OTH exome AF: 0.000770

GnomAD4 genome AF: 0.000717 AC: 109 AN: 152056 Hom.: 0 Cov.: 33 AF XY: 0.000619 AC XY: 46 AN XY: 74336

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00284

Gnomad4 NFE AF: 0.000927

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000610 Hom.: 0

Bravo AF: 0.000612

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 27, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 07, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.016
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201725633; hg19: chr19-1622039;