15-56921008-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.533

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]

ACMG classification

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	UniProt
TCF12	NM_207037.2	c.76-18A>G		intron_variant		ENST00000333725.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF12	ENST00000333725.10	c.76-18A>G		intron_variant		1	NM_207037.2	P4

Frequencies

GnomAD3 genomes AF: 0.00448 AC: 681 AN: 152122 Hom.: 6 Cov.: 32

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.: 71 AF XY: 0.00795 AC XY: 1011 AN XY: 127154

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.: 84 Cov.: 28 AF XY: 0.00361 AC XY: 2573 AN XY: 712412

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.: 8 Cov.: 32 AF XY: 0.00506 AC XY: 377 AN XY: 74442

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.: 2

Bravo AF: 0.00776

Asia WGS AF: 0.00809 AC: 28 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 16, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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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

Other links and lift over

dbSNP: rs75960447; hg19: chr15-57213206;