rs201725633

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.67

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal agammaglobulinemia
Inheritance: SD, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
agammaglobulinemia 8, autosomal dominant
Inheritance: AR, AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

TCF3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000717 (109/152056) while in subpopulation NFE AF = 0.000927 (63/67948). AF 95% confidence interval is 0.000743. There are 0 homozygotes in GnomAd4. There are 46 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD,SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCF3	NM_003200.5 link	c.822+14C>T		intron_variant	Intron 10 of 18	ENST00000262965.12	NP_003191.1	P15923-1
TCF3	NM_001136139.4 link	c.822+14C>T		intron_variant	Intron 10 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.822+14C>T		intron_variant	Intron 10 of 18	1	NM_003200.5	ENSP00000262965.5		P15923-1
TCF3	ENST00000588136.7 link	c.822+14C>T		intron_variant	Intron 10 of 19	2	NM_001136139.4	ENSP00000468487.1		P15923-2

Frequencies

GnomAD3 genomes

AF:

0.000717

AC:

109

AN:

151938

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00108

AC:

233

AN:

214930

AF XY:

0.00107

show subpopulations

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 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.:

Cov.:

AF XY:

0.000837

AC XY:

601

AN XY:

718328

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33290

American (AMR)

AF:

0.000695

AC:

AN:

43184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25696

East Asian (EAS)

AF:

0.00

AC:

AN:

39158

South Asian (SAS)

AF:

0.00

AC:

AN:

83836

European-Finnish (FIN)

AF:

0.00427

AC:

215

AN:

50390

Middle Eastern (MID)

AF:

0.000188

AC:

AN:

5306

European-Non Finnish (NFE)

AF:

0.000889

AC:

983

AN:

1106348

Other (OTH)

AF:

0.000770

AC:

AN:

59766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

148

221

295

369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000717

AC:

109

AN:

152056

Hom.:

Cov.:

AF XY:

0.000619

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41478

American (AMR)

AF:

0.000588

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00284

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000927

AC:

AN:

67948

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000610

Hom.:

Bravo

AF:

0.000612

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 27, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.016

(source)

DANN

Benign

0.45

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over