Variant chr15-56920030-TTTTG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_207037.2(TCF12):c.75+62_75+65del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,605,228 control chromosomes in the GnomAD database, including 1,417 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.028 ( 71 hom., cov: 30)

Exomes 𝑓: 0.039 ( 1346 hom. )

Consequence

TCF12
NM_207037.2 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.54

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 15-56920030-TTTTG-T is Benign according to our data. Variant chr15-56920030-TTTTG-T is described in ClinVar as [Likely_benign]. Clinvar id is 1326658.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-56920030-TTTTG-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0282 (4283/151920) while in subpopulation NFE AF= 0.0441 (2995/67914). AF 95% confidence interval is 0.0428. There are 71 homozygotes in gnomad4. There are 2008 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4283 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF12	NM_207037.2 linkuse as main transcript	c.75+62_75+65del		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.75+62_75+65del		intron_variant		1	NM_207037.2	ENSP00000331057	P4	Q99081-3

Frequencies

GnomAD3 genomes

AF:

0.0282

AC:

4281

AN:

151802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00786

Gnomad AMI

AF:

0.0837

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0163

Gnomad FIN

AF:

0.0224

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0441

Gnomad OTH

AF:

0.0197

GnomAD3 exomes

AF:

0.0271

AC:

6691

AN:

246558

Hom.:

129

AF XY:

0.0277

AC XY:

3692

AN XY:

133210

show subpopulations

Gnomad AFR exome

AF:

0.00785

Gnomad AMR exome

AF:

0.0189

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.00188

Gnomad SAS exome

AF:

0.0146

Gnomad FIN exome

AF:

0.0236

Gnomad NFE exome

AF:

0.0416

Gnomad OTH exome

AF:

0.0292

GnomAD4 exome

AF:

0.0390

AC:

56612

AN:

1453308

Hom.:

1346

AF XY:

0.0387

AC XY:

27967

AN XY:

723396

show subpopulations

Gnomad4 AFR exome

AF:

0.00567

Gnomad4 AMR exome

AF:

0.0200

Gnomad4 ASJ exome

AF:

0.0146

Gnomad4 EAS exome

AF:

0.000935

Gnomad4 SAS exome

AF:

0.0155

Gnomad4 FIN exome

AF:

0.0232

Gnomad4 NFE exome

AF:

0.0458

Gnomad4 OTH exome

AF:

0.0313

GnomAD4 genome

AF:

0.0282

AC:

4283

AN:

151920

Hom.:

Cov.:

AF XY:

0.0270

AC XY:

2008

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.00784

Gnomad4 AMR

AF:

0.0314

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0169

Gnomad4 FIN

AF:

0.0224

Gnomad4 NFE

AF:

0.0441

Gnomad4 OTH

AF:

0.0194

Bravo

AF:

0.0277

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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