15-56920030-TTTTG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54

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 -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 GnomAd at 4281 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF12	NM_207037.2	c.75+62_75+65del		intron_variant		ENST00000333725.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF12	ENST00000333725.10	c.75+62_75+65del		intron_variant		1	NM_207037.2	P4

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4281 AN: 151802 Hom.: 71 Cov.: 30

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

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

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.: 71 Cov.: 30 AF XY: 0.0270 AC XY: 2008 AN XY: 74242

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

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

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

Other links and lift over

dbSNP: rs527665020; hg19: chr15-57212228;