Variant rs75960447 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207037.2(TCF12):c.76-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 1,585,544 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 84 hom. )

Consequence

TCF12
NM_207037.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.533

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=-0.88).

BP6

Variant 15-56921008-A-G is Benign according to our data. Variant chr15-56921008-A-G is described in ClinVar as [Benign]. Clinvar id is 263283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF12	NM_207037.2 linkuse as main transcript	c.76-18A>G		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.76-18A>G		intron_variant		1	NM_207037.2	ENSP00000331057	P4	Q99081-3

Frequencies

GnomAD3 genomes

AF:

0.00448

AC:

681

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00750

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00241

Gnomad OTH

AF:

0.00959

GnomAD3 exomes

AF:

0.0103

AC:

2410

AN:

235026

Hom.:

AF XY:

0.00795

AC XY:

1011

AN XY:

127154

show subpopulations

Gnomad AFR exome

AF:

0.00244

Gnomad AMR exome

AF:

0.0636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00861

Gnomad SAS exome

AF:

0.000565

Gnomad FIN exome

AF:

0.00156

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.00758

GnomAD4 exome

AF:

0.00395

AC:

5667

AN:

1433306

Hom.:

Cov.:

AF XY:

0.00361

AC XY:

2573

AN XY:

712412

show subpopulations

Gnomad4 AFR exome

AF:

0.00248

Gnomad4 AMR exome

AF:

0.0558

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00733

Gnomad4 SAS exome

AF:

0.000408

Gnomad4 FIN exome

AF:

0.00170

Gnomad4 NFE exome

AF:

0.00240

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.00456

AC:

694

AN:

152238

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00286

Gnomad4 AMR

AF:

0.0218

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00752

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00241

Gnomad4 OTH

AF:

0.00949

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.00776

Asia WGS

AF:

0.00809

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 16, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

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

-0.88

CADD

Benign

4.0

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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