15-56919800-C-G

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.-22-92C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,166,340 control chromosomes in the GnomAD database, including 91 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 (47 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (44 hom.)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.951

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=-0.8).
• BP6: Variant 15-56919800-C-G is Benign according to our data. Variant chr15-56919800-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1186674.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1939/152178) while in subpopulation AFR AF= 0.0404 (1677/41528). AF 95% confidence interval is 0.0388. There are 47 homozygotes in gnomad4. There are 888 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 1920 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF12	NM_207037.2	c.-22-92C>G		intron_variant		ENST00000333725.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF12	ENST00000333725.10	c.-22-92C>G		intron_variant		1	NM_207037.2	P4

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1920 AN: 152062 Hom.: 44 Cov.: 31

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.00256 AC: 2592 AN: 1014162 Hom.: 44 Cov.: 12 AF XY: 0.00248 AC XY: 1277 AN XY: 514164

Gnomad4 AFR exome AF: 0.0407

Gnomad4 AMR exome AF: 0.00302

Gnomad4 ASJ exome AF: 0.0498

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000337

Gnomad4 OTH exome AF: 0.00588

GnomAD4 genome AF: 0.0127 AC: 1939 AN: 152178 Hom.: 47 Cov.: 31 AF XY: 0.0119 AC XY: 888 AN XY: 74394

Gnomad4 AFR AF: 0.0404

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00324 Hom.: 0

Bravo AF: 0.0145

Asia WGS AF: 0.00375 AC: 13 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

Jan 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.6
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs114409025; hg19: chr15-57211998;