Variant chr15-56919764-G-A 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 NM_207037.2(TCF12):c.-22-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 742,728 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 25 hom., cov: 31)

Exomes 𝑓: 0.016 ( 103 hom. )

Consequence

TCF12
NM_207037.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.835

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=-0.75).

BP6

Variant 15-56919764-G-A is Benign according to our data. Variant chr15-56919764-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1213259.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 = 0.0134 (2042/152116) while in subpopulation NFE AF= 0.0208 (1412/67962). AF 95% confidence interval is 0.0199. There are 25 homozygotes in gnomad4. There are 1019 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2042 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF12	NM_207037.2 linkuse as main transcript	c.-22-128G>A		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.-22-128G>A		intron_variant		1	NM_207037.2	ENSP00000331057	P4	Q99081-3

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2042

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00771

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0212

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.0208

Gnomad OTH

AF:

0.0125

GnomAD4 exome

AF:

0.0164

AC:

9676

AN:

590612

Hom.:

103

Cov.:

AF XY:

0.0155

AC XY:

4762

AN XY:

306248

show subpopulations

Gnomad4 AFR exome

AF:

0.00383

Gnomad4 AMR exome

AF:

0.00884

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.0000358

Gnomad4 SAS exome

AF:

0.00232

Gnomad4 FIN exome

AF:

0.0256

Gnomad4 NFE exome

AF:

0.0195

Gnomad4 OTH exome

AF:

0.0142

GnomAD4 genome

AF:

0.0134

AC:

2042

AN:

152116

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1019

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00320

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.0212

Gnomad4 NFE

AF:

0.0208

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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