Variant rs117914532 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000333725.10(TCF12):c.580-12T>C variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00867 in 1,581,168 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0087 ( 62 hom. )

Consequence

TCF12
ENST00000333725.10 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.009539

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.94

Variant links:

Genes affected

TCF12 (HGNC:11623): (transcription factor 12) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

TCF12 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=-0.56).

BP6

Variant 15-57231140-T-C is Benign according to our data. Variant chr15-57231140-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 263282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-57231140-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0079 (1202/152224) while in subpopulation NFE AF= 0.0108 (732/67970). AF 95% confidence interval is 0.0101. There are 7 homozygotes in gnomad4. There are 626 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1202 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF12	NM_207037.2 linkuse as main transcript	c.580-12T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000333725.10	NP_996920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF12	ENST00000333725.10 linkuse as main transcript	c.580-12T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_207037.2	ENSP00000331057	P4	Q99081-3

Frequencies

GnomAD3 genomes

AF:

0.00791

AC:

1203

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00571

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0277

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00748

AC:

1874

AN:

250584

Hom.:

AF XY:

0.00738

AC XY:

1000

AN XY:

135472

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00206

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0260

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00769

GnomAD4 exome

AF:

0.00875

AC:

12502

AN:

1428944

Hom.:

Cov.:

AF XY:

0.00849

AC XY:

6054

AN XY:

712938

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000187

Gnomad4 FIN exome

AF:

0.0245

Gnomad4 NFE exome

AF:

0.00974

Gnomad4 OTH exome

AF:

0.00670

GnomAD4 genome

AF:

0.00790

AC:

1202

AN:

152224

Hom.:

Cov.:

AF XY:

0.00841

AC XY:

626

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00570

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0277

Gnomad4 NFE

AF:

0.0108

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00871

Hom.:

Bravo

AF:

0.00614

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 09, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 21, 2020	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0095

dbscSNV1_RF

Benign

0.14

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

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