15-56919764-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.835

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 -14 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_single_submitter, 1 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 GnomAd at 2042 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF12	NM_207037.2	c.-22-128G>A		intron_variant		ENST00000333725.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF12	ENST00000333725.10	c.-22-128G>A		intron_variant		1	NM_207037.2	P4

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2042 AN: 151998 Hom.: 25 Cov.: 31

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.: 8 AF XY: 0.0155 AC XY: 4762 AN XY: 306248

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.: 25 Cov.: 31 AF XY: 0.0137 AC XY: 1019 AN XY: 74362

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.: 2

Bravo AF: 0.0123

Asia WGS AF: 0.00260 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	10
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

Other links and lift over

dbSNP: rs186997278; hg19: chr15-57211962;